Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People with Obesity

Circulation

Volumn 137, Issue 15, 2018, Pages 1614-1631

  Packer, Milton ^a  

^a BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

aldosterone; heart failure; leptin; neprilysin; obesity

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; ALDOSTERONE; LEPTIN; MEMBRANE METALLOENDOPEPTIDASE; NATRIURETIC FACTOR; LEP PROTEIN, HUMAN;

ARTICLE; COMORBIDITY; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; EPICARDIAL FAT; HEART FAILURE; HUMAN; NONHUMAN; OBESITY; PATHOGENESIS; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; ADIPOSE TISSUE; ADRENERGIC SYSTEM; HEART LEFT VENTRICLE FUNCTION; HEART STROKE VOLUME; HEART VENTRICLE; INNERVATION; METABOLISM; PROGNOSIS; RISK FACTOR;

ADIPOSE TISSUE; ADIPOSITY; ALDOSTERONE; HEART FAILURE; HEART VENTRICLES; HUMANS; LEPTIN; NEPRILYSIN; OBESITY; PHENOTYPE; PROGNOSIS; RISK FACTORS; SIGNAL TRANSDUCTION; STROKE VOLUME; SYMPATHETIC NERVOUS SYSTEM; VENTRICULAR FUNCTION, LEFT;

EID: 85051630695     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.117.032474     Document Type: Article

References (320)

1. Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, Kannel WB, Vasan RS, Obesity and the risk of heart failure. N Engl J Med 2002 347 305 313. doi: 10.1056/NEJMoa020245.
2. Chen YT, Vaccarino V, Williams CS, Butler J, Berkman LF, Krumholz HM, Risk factors for heart failure in the elderly: a prospective community-based study. Am J Med 1999 106 605 612
3. Alpert MA, Terry BE, Mulekar M, Cohen MV, Massey CV, Fan TM, Panayiotou H, Mukerji V, Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss. Am J Cardiol 1997 80 736 740
4. Sundström J, Bruze G, Ottosson J, Marcus C, Näslund I, Neovius M, Weight loss and heart failure: a nationwide study of gastric bypass surgery versus intensive lifestyle treatment. Circulation 2017 135 1577 1585. doi: 10.1161/CIRCULATIONAHA.116.025629.
5. Udell JA, Cavender MA, Bhatt DL, Chatterjee S, Farkouh ME, Scirica BM, Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol 2015 3 356 366. doi: 10.1016/S2213-8587(15)00044-3.
6. Oreopoulos A, Ezekowitz JA, McAlister FA, Kalantar-Zadeh K, Fonarow GC, Norris CM, Johnson JA, Padwal RS, Association between direct measures of body composition and prognostic factors in chronic heart failure. Mayo Clin Proc 2010 85 609 617. doi: 10.4065/mcp.2010.0103.
7. Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA, Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation 2017 136 6 19. doi: 10.1161/CIRCULATIONAHA.116.026807.
8. Reddy YN, Melenovsky V, Redfield MM, Nishimura RA, Borlaug BA, High-output heart failure: a 15-year experience. J Am Coll Cardiol 2016 68 473 482. doi: 10.1016/j.jacc.2016.05.043.
9. Licata G, Scaglione R, Barbagallo M, Parrinello G, Capuana G, Lipari R, Merlino G, Ganguzza A, Effect of obesity on left ventricular function studied by radionuclide angiocardiography. Int J Obes 1991 15 295 302
10. Bentley-Lewis R, Adler GK, Perlstein T, Seely EW, Hopkins PN, Williams GH, Garg R, Body mass index predicts aldosterone production in normotensive adults on a high-salt diet. J Clin Endocrinol Metab 2007 92 4472 4475. doi: 10.1210/jc.2007-1088.
11. Goodfriend TL, Kelley DE, Goodpaster BH, Winters SJ, Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women. Obes Res 1999 7 355 362
12. Vatutin NT, Shevelok AN, Relationship between blood aldosterone and somatometric parameters in patients with chronic heart failure and preserved ejection fraction of left ventricle. Klin Med (Mosk) 2016 94 265 269
13. Di Bello V, Santini F, Di Cori A, Pucci A, Palagi C, Delle Donne MG, Fierabracci P, Marsili A, Talini E, Giannetti M, Biadi O, Balbarini A, Mariani M, Pinchera A, Obesity cardiomyopathy: is it a reality? An ultrasonic tissue characterization study. J Am Soc Echocardiogr 2006 19 1063 1071. doi: 10.1016/j.echo.2006.03.033.
14. Gupta A, Braunwald E, McNulty S, Felker GM, Gilbert EM, Alharethi R, Lee KL, Anstrom KJ, Redfield MM, Goldsmith SR, O'Connor CM, Bull DA, Stehlik J, Litwin SE, Obesity and the response to intensified diuretic treatment in decompensated heart failure: a DOSE trial substudy. J Card Fail 2012 18 837 844. doi: 10.1016/j.cardfail.2012.09.005.
15. Kasper EK, Hruban RH, Baughman KL, Cardiomyopathy of obesity: a clinicopathologic evaluation of 43 obese patients with heart failure. Am J Cardiol 1992 70 921 924
16. Maurer MS, King DL, El-Khoury Rumbarger L, Packer M, Burkhoff D, Left heart failure with a normal ejection fraction: identification of different pathophysiologic mechanisms. J Card Fail 2005 11 177 187
17. Abramov D, He KL, Wang J, Burkhoff D, Maurer MS, The impact of extra cardiac comorbidities on pressure volume relations in heart failure and preserved ejection fraction. J Card Fail 2011 17 547 555. doi: 10.1016/j.cardfail.2011.03.010.
18. Burkhoff D, Maurer MS, Packer M, Heart failure with a normal ejection fraction: is it really a disorder of diastolic function? Circulation 2003 107 656 658
19. Maurer MS, Burkhoff D, Fried LP, Gottdiener J, King DL, Kitzman DW, Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study. J Am Coll Cardiol 2007 49 972 981. doi: 10.1016/j.jacc.2006.10.061.
20. Faxén UL, Hage C, Andreasson A, Donal E, Daubert JC, Linde C, Brismar K, Lund LH, HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin. Int J Cardiol 2017 228 709 716. doi: 10.1016/j.ijcard.2016.11.194.
21. Wei J, Nelson MD, Szczepaniak EW, Smith L, Mehta PK, Thomson LE, Berman DS, Li D, Bairey Merz CN, Szczepaniak LS, Myocardial steatosis as a possible mechanistic link between diastolic dysfunction and coronary microvascular dysfunction in women. Am J Physiol Heart Circ Physiol 2016 310 H14 H19. doi: 10.1152/ajpheart.00612.2015.
22. Zyatenkova E, Drapkina O, Ivashkin V, Characteristics of vessels wall, myocardium and epicardial fat in patients with heart failure with preserved ejection fraction with and without metabolic syndrome. Endosc Ultrasound 2014 3 Suppl 1 S1 S2
23. Tromp J, Khan MA, Klip IT, Meyer S, de Boer RA, Jaarsma T, Hillege H, van Veldhuisen DJ, van der Meer P, Voors AA, Biomarker profiles in heart failure patients with preserved and reduced ejection fraction. J Am Heart Assoc 2017; 6 pii: e003989. doi: 10.1161/JAHA.116.003989.
24. Patel VB, Mori J, McLean BA, Basu R, Das SK, Ramprasath T, Parajuli N, Penninger JM, Grant MB, Lopaschuk GD, Oudit GY, ACE2 deficiency worsens epicardial adipose tissue inflammation and cardiac dysfunction in response to diet-induced obesity. Diabetes 2016 65 85 95. doi: 10.2337/db15-0399.
25. Essick EE, Sam F, Cardiac hypertrophy and fibrosis in the metabolic syndrome: a role for aldosterone and the mineralocorticoid receptor. Int J Hypertens 2011 2011 346985. doi: 10.4061/2011/346985.
26. Minnaard-Huiban M, Hermans JJ, Essen Hv, Bitsch N, Smits JF, Comparison of the effects of intrapericardial and intravenous aldosterone infusions on left ventricular fibrosis in rats. Eur J Heart Fail 2008 10 1166 1171. doi: 10.1016/j.ejheart.2008.09.012.
27. Borlaug BA, Carter RE, Melenovsky V, DeSimone CV, Gaba P, Killu A, Naksuk N, Lerman L, Asirvatham SJ, Percutaneous pericardial resection: a novel potential treatment for heart failure with preserved ejection fraction. Circ Heart Fail 2017 10 e003612. doi: 10.1161/CIRCHEARTFAILURE.116.003612.
28. Altun I, Unal Y, Basaran O, Akin F, Emir GK, Kutlu G, Biteker M, Increased epicardial fat thickness correlates with aortic stiffness and N-terminal pro-brain natriuretic peptide levels in acute ischemic stroke patients. Tex Heart Inst J 2016 43 220 226. doi: 10.14503/THIJ-15-5428.
29. Lin YK, Chen YC, Chang SL, Lin YJ, Chen JH, Yeh YH, Chen SA, Chen YJ, Heart failure epicardial fat increases atrial arrhythmogenesis. Int J Cardiol 2013 167 1979 1983. doi: 10.1016/j.ijcard.2012.05.009.
30. Hohl M, Lau DH, Müller A, Elliott AD, Linz B, Mahajan R, Hendriks JML, Böhm M, Schotten U, Sanders P, Linz D, Concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype in male hypertensive rats. J Am Heart Assoc 2017 6 9 e006717. doi: 10.1161/JAHA.117.006717.
31. Tsujimoto T, Kajio H, Abdominal obesity is associated with an increased risk of all-cause mortality in patients with HFpEF. J Am Coll Cardiol 2017 70 2739 2749. doi: 10.1016/j.jacc.2017.09.1111.
32. Hoppmann J, Perwitz N, Meier B, Fasshauer M, Hadaschik D, Lehnert H, Klein J, The balance between gluco-and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol 2010 204 153 164. doi: 10.1677/JOE-09-0292.
33. Bender SB, DeMarco VG, Padilla J, Jenkins NT, Habibi J, Garro M, Pulakat L, Aroor AR, Jaffe IZ, Sowers JR, Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction. Hypertension 2015 65 1082 1088. doi: 10.1161/HYPERTENSIONAHA.114.04912.
34. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O'Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM, TOPCAT Investigators Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014 370 1383 1392. doi: 10.1056/NEJMoa1313731.
35. Anand IS, Claggett B, Liu J, Shah AM, Rector TS, Shah SJ, Desai AS, O'Meara E, Fleg JL, Pfeffer MA, Pitt B, Solomon SD, Interaction between spironolactone and natriuretic peptides in patients with heart failure and preserved ejection fraction: from the TOPCAT trial. JACC Heart Fail 2017 5 241 252. doi: 10.1016/j.jchf.2016.11.015.
36. Anand IS, Rector TS, Cleland JG, Kuskowski M, McKelvie RS, Persson H, McMurray JJ, Zile MR, Komajda M, Massie BM, Carson PE, Prognostic value of baseline plasma amino-terminal pro-brain natriuretic peptide and its interactions with irbesartan treatment effects in patients with heart failure and preserved ejection fraction: findings from the I-PRESERVE trial. Circ Heart Fail 2011 4 569 577. doi: 10.1161/CIRCHEARTFAILURE.111.962654.
37. Ho JE, McCabe EL, Wang TJ, Larson MG, Levy D, Tsao C, Aragam J, Mitchell GF, Benjamin EJ, Vasan RS, Cheng S, Cardiometabolic traits and systolic mechanics in the community. Circ Heart Fail 2017 10 5 e003536. doi: 10.1161/CIRCHEARTFAILURE.116.003536.
38. Vest AR, Patel P, Schauer PR, Satava ME, Cavalcante JL, Brethauer S, Young JB, Clinical and echocardiographic outcomes after bariatric surgery in obese patients with left ventricular systolic dysfunction. Circ Heart Fail 2016 Mar 9 3 e002260. doi: 10.1161/CIRCHEARTFAILURE. 115.002260.
39. Wong C, Marwick TH, Obesity cardiomyopathy: pathogenesis and pathophysiology. Nat Clin Pract Cardiovasc Med 2007 4 436 443. doi: 10.1038/ncpcardio0943.
40. Wu CK, Tsai HY, Su MM, Wu YF, Hwang JJ, Lin JL, Lin LY, Chen JJ, Evolutional change in epicardial fat and its correlation with myocardial diffuse fibrosis in heart failure patients. J Clin Lipidol 2017 11 1421 1431. doi: 10.1016/j.jacl.2017.08.018.
41. Abbasi SA, Hundley WG, Bluemke DA, Jerosch-Herold M, Blankstein R, Petersen SE, Rider OJ, Lima JA, Allison MA, Murthy VL, Shah RV, Visceral adiposity and left ventricular remodeling: the Multi-Ethnic Study of Atherosclerosis. Nutr Metab Cardiovasc Dis 2015 25 667 676. doi: 10.1016/j.numecd.2015.03.016.
42. Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S, Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 2007 56 1010 1013. doi: 10.2337/db06-1656.
43. Catena C, Colussi G, Brosolo G, Novello M, Sechi LA, Aldosterone and left ventricular remodeling. Horm Metab Res 2015 47 981 986. doi: 10.1055/s-0035-1565055.
44. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J, The effect of spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999 341 709 717. doi: 10.1056/NEJM199909023411001.
45. Olivier A, Pitt B, Girerd N, Lamiral Z, Machu JL, McMurray JJV, Swedberg K, van Veldhuisen DJ, Collier TJ, Pocock SJ, Rossignol P, Zannad F, Pizard A, Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity: insight from the EMPHASIS-HF trial. Eur J Heart Fail 2017 19 1186 1197. doi: 10.1002/ejhf.792.
46. Persson CE, Björck L, Lagergren J, Lappas G, Giang KW, Rosengren A, Risk of heart failure in obese patients with and without bariatric surgery in Sweden: a registry-based study. J Card Fail 2017 23 530 537. doi: 10.1016/j.cardfail.2017.05.005.
47. Alpert MA, Pritchett AM, Bariatric surgery in patients with left ventricular systolic dysfunction: effective, but is it safe? Circ Heart Fail 2016 9 e002960. doi: 10.1161/CIRCHEARTFAILURE.116.002960.
48. Karayannis G, Giamouzis G, Tziolas N, Georgoulias P, Skoularigis J, Mikhailidis DP, Triposkiadis F, Association between epicardial fat thickness and weight homeostasis hormones in patients with noncachectic heart failure. Angiology 2013 64 173 180. doi: 10.1177/0003319712447978.
49. López-Jaramillo P, Gómez-Arbeláez D, López-López J, López-López C, Martínez-Ortega J, Gómez-Rodríguez A, Triana-Cubillos S, The role of leptin/adiponectin ratio in metabolic syndrome and diabetes. Horm Mol Biol Clin Investig 2014 18 37 45. doi: 10.1515/hmbci-2013-0053.
50. Dutheil F, Gordon BA, Naughton G, Crendal E, Courteix D, Chaplais E, Thivel D, Lac G, Benson AC, Cardiovascular risk of adipokines: a review. J Int Med Res 2017 Jan 1 300060517706578. doi: 10.1177/0300060517706578.
51. Kim SJ, Kim HS, Jung JW, Kim NS, Noh CI, Hong YM, Correlation between epicardial fat thickness by echocardiography and other parameters in obese adolescents. Korean Circ J 2012 42 471 478. doi: 10.4070/kcj.2012.42.7.471.
52. Trayhurn P, Wood IS, Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004 92 347 355
53. Martínez-Martínez E, Jurado-López R, Cervantes-Escalera P, Cachofeiro V, Miana M, Leptin, a mediator of cardiac damage associated with obesity. Horm Mol Biol Clin Investig 2014 18 3 14. doi: 10.1515/hmbci-2013-0060.
54. Weigle DS, Bukowski TR, Foster DC, Holderman S, Kramer JM, Lasser G, Lofton-Day CE, Prunkard DE, Raymond C, Kuijper JL, Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest 1995 96 2065 2070. doi: 10.1172/JCI118254.
55. Pandit R, Beerens S, Adan RAH, Role of leptin in energy expenditure: the hypothalamic perspective. Am J Physiol Regul Integr Comp Physiol 2017 312 R938 R947. doi: 10.1152/ajpregu.00045.2016.
56. Toth MJ, Gottlieb SS, Fisher ML, Ryan AS, Nicklas BJ, Poehlman ET, Plasma leptin concentrations and energy expenditure in heart failure patients. Metabolism 1997 46 450 453
57. Lund LH, Freda P, Williams JJ, LaManca JJ, LeJemtel TH, Mancini DM, Leptin resistance after heart transplantation. Eur J Heart Fail 2010 12 516 520. doi: 10.1093/eurjhf/hfq026.
58. Karmazyn M, Gan XT, Rajapurohitam V, The potential contribution of circulating and locally produced leptin to cardiac hypertrophy and failure. Can J Physiol Pharmacol 2013 91 883 888. doi: 10.1139/cjpp-2013-0057.
59. Ren J, Ma H, Impaired cardiac function in leptin-deficient mice. Curr Hypertens Rep 2008 10 448 453
60. Thakker GD, Frangogiannis NG, Bujak M, Zymek P, Gaubatz JW, Reddy AK, Taffet G, Michael LH, Entman ML, Ballantyne CM, Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction. Am J Physiol Heart Circ Physiol 2006 291 H2504 H2514. doi: 10.1152/ajpheart.00322.2006.
61. Dong F, Zhang X, Yang X, Esberg LB, Yang H, Zhang Z, Culver B, Ren J, Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice. J Endocrinol 2006 188 25 36. doi: 10.1677/joe.1.06241.
62. Gómez-Hurtado N, Domínguez-Rodríguez A, Mateo P, Fernández-Velasco M, Val-Blasco A, Aizpún R, Sabourin J, Gómez AM, Benitah JP, Delgado C, Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse. J Physiol 2017 595 4227 4243. doi: 10.1113/JP274030.
63. McGaffin KR, Sun CK, Rager JJ, Romano LC, Zou B, Mathier MA, O'Doherty RM, McTiernan CF, O'Donnell CP, Leptin signalling reduces the severity of cardiac dysfunction and remodelling after chronic ischaemic injury. Cardiovasc Res 2008 77 54 63. doi: 10.1093/cvr/cvm023.
64. Trivedi P, Yang R, Barouch LA, Decreased p110alpha catalytic activity accompanies increased myocyte apoptosis and cardiac hypertrophy in leptin deficient ob/ob mice. Cell Cycle 2008 7 560 565. doi: 10.4161/cc.7.5.5529.
65. Hall ME, Smith G, Hall JE, Stec DE, Cardiomyocyte-specific deletion of leptin receptors causes lethal heart failure in Cre-recombinase-mediated cardiotoxicity. Am J Physiol Regul Integr Comp Physiol 2012 303 R1241 R1250. doi: 10.1152/ajpregu.00292.2012.
66. McGaffin KR, Witham WG, Yester KA, Romano LC, O'Doherty RM, McTiernan CF, O'Donnell CP, Cardiac-specific leptin receptor deletion exacerbates ischaemic heart failure in mice. Cardiovasc Res 2011 89 60 71. doi: 10.1093/cvr/cvq288.
67. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, Lubina JA, Patane J, Self B, Hunt P, McCamish M, Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999 282 1568 1575
68. Mark AL, Selective leptin resistance revisited. Am J Physiol Regul Integr Comp Physiol 2013 305 R566 R581. doi: 10.1152/ajpregu.00180.2013.
69. Mark AL, Correia ML, Rahmouni K, Haynes WG, Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications. J Hypertens 2002 20 1245 1250
70. Sharma V, Mustafa S, Patel N, Wambolt R, Allard MF, McNeill JH, Stimulation of cardiac fatty acid oxidation by leptin is mediated by a nitric oxide-p38 MAPK-dependent mechanism. Eur J Pharmacol 2009 617 113 117. doi: 10.1016/j.ejphar.2009.06.037.
71. Wold LE, Relling DP, Duan J, Norby FL, Ren J, Abrogated leptin-induced cardiac contractile response in ventricular myocytes under spontaneous hypertension: role of Jak/STAT pathway. Hypertension 2002 39 69 74
72. Ren J, Zhu BH, Relling DP, Esberg LB, Ceylan-Isik AF, High-fat diet-induced obesity leads to resistance to leptin-induced cardiomyocyte contractile response. Obesity (Silver Spring) 2008 16 2417 2423. doi: 10.1038/oby.2008.381.
73. Radin MJ, Holycross BJ, McCune SA, Altschuld RA, Crosstalk between leptin and interleukin-1β abrogates negative inotropic effects in a model of chronic hyperleptinemia. Exp Biol Med (Maywood) 2011 236 1263 1273. doi: 10.1258/ebm.2011.011144.
74. Mitchell JL, Morgan DA, Correia ML, Mark AL, Sivitz WI, Haynes WG, Does leptin stimulate nitric oxide to oppose the effects of sympathetic activation? Hypertension 2001 38 1081 1086
75. Nascimento TB, Baptista Rde F, Pereira PC, Campos DH, Leopoldo AS, Leopoldo AP, Oliveira Júnior SA, Padovani CR, Cicogna AC, Cordellini S, Vascular alterations in high-fat diet-obese rats: role of endothelial L-arginine/NO pathway. Arq Bras Cardiol 2011 97 40 45
76. Bełtowski J, Wójcicka G, Jamroz-Wiśniewska A, Role of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the regulation of blood pressure by leptin in lean and obese rats. Life Sci 2006 79 63 71. doi: 10.1016/j.lfs.2005.12.041.
77. Villarreal D, Reams G, Samar H, Spear R, Freeman RH, Effects of chronic nitric oxide inhibition on the renal excretory response to leptin. Obes Res 2004 12 1006 1010. doi: 10.1038/oby.2004.123.
78. Bełtowski J, Wjcicka G, Górny D, Marciniak A, Human leptin administered intraperitoneally stimulates natriuresis and decreases renal medullary Na+/K+-ATPase activity in the rat: impaired effect in dietary-induced obesity. Med Sci Monit 2002 8 BR221 BR229
79. Stucchi P, Guzmán-Ruiz R, Gil-Ortega M, Merino B, Somoza B, Cano V, de Castro J, Sevillano J, Ramos MP, Fernández-Alfonso MS, Ruiz-Gayo M, Leptin resistance develops spontaneously in mice during adult life in a tissue-specific manner: consequences for hepatic steatosis. Biochimie 2011 93 1779 1785. doi: 10.1016/j.biochi.2011.06.020.
80. Leifheit-Nestler M, Wagner NM, Gogiraju R, Didié M, Konstantinides S, Hasenfuss G, Schäfer K, Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity. J Transl Med 2013 11 170. doi: 10.1186/1479-5876-11-170.
81. Somoza B, Guzmán R, Cano V, Merino B, Ramos P, Díez-Fernández C, Fernández-Alfonso MS, Ruiz-Gayo M, Induction of cardiac uncoupling protein-2 expression and adenosine 5'-monophosphate-activated protein kinase phosphorylation during early states of diet-induced obesity in mice. Endocrinology 2007 148 924 931. doi: 10.1210/en.2006-0914.
82. Bełtowski J, Leptin and the regulation of renal sodium handling and renal Na-transporting ATPases: role in the pathogenesis of arterial hypertension. Curr Cardiol Rev 2010 6 31 40. doi: 10.2174/157340310790231644.
83. Lohmeier TE, Iliescu R, The sympathetic nervous system in obesity hypertension. Curr Hypertens Rep 2013 15 409 416. doi: 10.1007/s11906-013-0356-1.
84. Barnes MJ, McDougal DH, Leptin into the rostral ventral lateral medulla (RVLM) augments renal sympathetic nerve activity and blood pressure. Front Neurosci 2014 8 232. doi: 10.3389/fnins.2014.00232.
85. Xue B, Yu Y, Zhang Z, Guo F, Beltz TG, Thunhorst RL, Felder RB, Johnson AK, Leptin mediates high-fat diet sensitization of angiotensin II-elicited hypertension by upregulating the brain renin-angiotensin system and inflammation. Hypertension 2016 67 970 976. doi: 10.1161/HYPERTENSIONAHA.115.06736.
86. Faulkner JL, Bruder-Nascimento T, Belin de Chantemèle EJ, The regulation of aldosterone secretion by leptin: implications in obesity-related cardiovascular disease. Curr Opin Nephrol Hypertens 2018 Mar 27 63 69. doi: 10.1097/MNH.0000000000000384.
87. Xie D, Bollag WB, Obesity, hypertension and aldosterone: is leptin the link? J Endocrinol 2016 230 F7 F11. doi: 10.1530/JOE-16-0160.
88. Purdham DM, Zou MX, Rajapurohitam V, Karmazyn M, Rat heart is a site of leptin production and action. Am J Physiol Heart Circ Physiol 2004 287 H2877 H2884. doi: 10.1152/ajpheart.00499.2004.
89. Yiannakouris N, Melistas L, Yannakoulia M, Mungal K, Mantzoros CS, The-2548G/A polymorphism in the human leptin gene promoter region is associated with plasma free leptin levels; interaction with adiposity and gender in healthy subjects. Hormones (Athens) 2003 2 229 236
90. Abd El-Aziz TA, Mohamed RH, Mohamed RH, Pasha HF, Leptin, leptin gene and leptin receptor gene polymorphism in heart failure with preserved ejection fraction. Heart Vessels 2012 27 271 279
91. Lieb W, Sullivan LM, Harris TB, Roubenoff R, Benjamin EJ, Levy D, Fox CS, Wang TJ, Wilson PW, Kannel WB, Vasan RS, Plasma leptin levels and incidence of heart failure, cardiovascular disease, and total mortality in elderly individuals. Diabetes Care 2009 32 612 616. doi: 10.2337/dc08-1596.
92. Wannamethee SG, Shaper AG, Whincup PH, Lennon L, Sattar N, Obesity and risk of incident heart failure in older men with and without pre-existing coronary heart disease: does leptin have a role? J Am Coll Cardiol 2011 58 1870 1877. doi: 10.1016/j.jacc.2011.06.057.
93. Ritsinger V, Brismar K, Malmberg K, Mellbin L, Näsman P, Rydén L, Söderberg S, Tenerz Å Norhammar A, Elevated levels of adipokines predict outcome after acute myocardial infarction: a long-term follow-up of the Glucose Tolerance in Patients with Acute Myocardial Infarction cohort. Diab Vasc Dis Res 2017 14 77 87. doi: 10.1177/1479164116678156.
94. Puurunen VP, Kiviniemi A, Lepojärvi S, Piira OP, Hedberg P, Junttila J, Ukkola O, Huikuri H, Leptin predicts short-term major adverse cardiac events in patients with coronary artery disease. Ann Med 2017 49 448 454. doi: 10.1080/07853890.2017.1301678.
95. Bobbert P, Jenke A, Bobbert T, Kühl U, Rauch U, Lassner D, Scheibenbogen C, Poller W, Schultheiss HP, Skurk C, High leptin and resistin expression in chronic heart failure: adverse outcome in patients with dilated and inflammatory cardiomyopathy. Eur J Heart Fail 2012 14 1265 1275. doi: 10.1093/eurjhf/hfs111.
96. Schulze PC, Biolo A, Gopal D, Shahzad K, Balog J, Fish M, Siwik D, Colucci WS, Dynamics in insulin resistance and plasma levels of adipokines in patients with acute decompensated and chronic stable heart failure. J Card Fail 2011 17 1004 1011. doi: 10.1016/j.cardfail.2011.08.010.
97. Khan RS, Kato TS, Chokshi A, Chew M, Yu S, Wu C, Singh P, Cheema FH, Takayama H, Harris C, Reyes-Soffer G, Knöll R, Milting H, Naka Y, Mancini D, Schulze PC, Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: correction after ventricular assist device implantation. Circ Heart Fail 2012 5 340 348. doi: 10.1161/CIRCHEARTFAILURE.111.964031.
98. Schulze PC, Kratzsch J, Linke A, Schoene N, Adams V, Gielen S, Erbs S, Moebius-Winkler S, Schuler G, Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure. Eur J Heart Fail 2003 5 33 40
99. Wojciechowska C, Jacheć W, Romuk E, Nowalany-Kozielska E, Tomasik A, Siemińska L, The effect of BMI, serum leptin, and adiponectin levels on prognosis in patients with non-ischaemic dilated cardiomyopathy. Endokrynol Pol 2017 68 26 34. doi: 10.5603/EP.2017.0005.
100. Leyva F, Anker SD, Egerer K, Stevenson JC, Kox WJ, Coats AJ, Hyperleptinaemia in chronic heart failure: relationships with insulin. Eur Heart J 1998 19 1547 1551
101. Doehner W, Rauchhaus M, Godsland IF, Egerer K, Niebauer J, Sharma R, Cicoira M, Florea VG, Coats AJ, Anker SD, Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-alpha. Int J Cardiol 2002 83 73 81
102. McGaffin KR, Moravec CS, McTiernan CF, Leptin signaling in the failing and mechanically unloaded human heart. Circ Heart Fail 2009 2 676 683. doi: 10.1161/CIRCHEARTFAILURE.109.869909.
103. Filippatos GS, Tsilias K, Venetsanou K, Karambinos E, Manolatos D, Kranidis A, Antonellis J, Kardaras F, Anthopoulos L, Baltopoulos G, Leptin serum levels in cachectic heart failure patients. Relationship with tumor necrosis factor-alpha system. Int J Cardiol 2000 76 117 122
104. Murdoch DR, Rooney E, Dargie HJ, Shapiro D, Morton JJ, McMurray JJ, Inappropriately low plasma leptin concentration in the cachexia associated with chronic heart failure. Heart 1999 82 352 356
105. Hryniewicz K, Androne AS, Hudaihed A, Katz SD, Partial reversal of cachexia by beta-adrenergic receptor blocker therapy in patients with chronic heart failure. J Card Fail 2003 9 464 468
106. Hyltander A, Daneryd P, Sandström R, Körner U, Lundholm K, Beta-adrenoceptor activity and resting energy metabolism in weight losing cancer patients. Eur J Cancer 2000 36 330 334
107. Kovacić D, Marinsek M, Gobec L, Lainscak M, Podbregar M, Effect of selective and non-selective beta-blockers on body weight, insulin resistance and leptin concentration in chronic heart failure. Clin Res Cardiol 2008 97 24 31. doi: 10.1007/s00392-007-0571-3.
108. Clark AL, Coats AJS, Krum H, Katus HA, Mohacsi P, Salekin D, Schultz MK, Packer M, Anker SD, Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial. J Cachexia Sarcopenia Muscle 2017 8 549 556. doi: 10.1002/jcsm.12191.
109. Dornfeld LP, Maxwell MH, Waks A, Tuck M, Mechanisms of hypertension in obesity. Kidney Int Suppl 1987 22 S254 S258
110. Bickel CA, Verbalis JG, Knepper MA, Ecelbarger CA, Increased renal Na-K-ATPase, NCC, and beta-ENaC abundance in obese Zucker rats. Am J Physiol Renal Physiol 2001 281 F639 F648. doi: 10.1152/ajprenal.2001.281.4.F639.
111. Briffa JF, Grinfeld E, Jenkin KA, Mathai ML, Poronnik P, McAinch AJ, Hryciw DH, Diet induced obesity in rats reduces NHE3 and Na(+)/K(+)-ATPase expression in the kidney. Clin Exp Pharmacol Physiol 2015 42 1118 1126. doi: 10.1111/1440-1681.12452.
112. Jia G, Habibi J, Aroor AR, Hill MA, DeMarco VG, Lee LE, Ma L, Barron BJ, Whaley-Connell A, Sowers JR, Enhanced endothelium epithelial sodium channel signaling prompts left ventricular diastolic dysfunction in obese female mice. Metabolism 2018 78 69 79. doi: 10.1016/j.metabol.2017.08.008.
113. Kargi AY, Iacobellis G, Adipose tissue and adrenal glands: novel pathophysiological mechanisms and clinical applications. Int J Endocrinol 2014 2014 614074. doi: 10.1155/2014/614074.
114. Harrington M, Pond-Tor S, Boney CM, Role of epidermal growth factor and ErbB2 receptors in 3T3-L1 adipogenesis. Obesity (Silver Spring) 2007 15 563 571. doi: 10.1038/oby.2007.562.
115. Ferrari P, Ferrandi M, Valentini G, Bianchi G, Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+-ATPase alterations in ouabain and adducin-dependent hypertension. Am J Physiol Regul Integr Comp Physiol 2006 290 R529 R535. doi: 10.1152/ajpregu.00518.2005.
116. Kassab S, Kato T, Wilkins FC, Chen R, Hall JE, Granger JP, Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension 1995 25 4 Pt 2 893 897
117. Nishimoto M, Fujita T, Renal mechanisms of salt-sensitive hypertension: contribution of two steroid receptor-associated pathways. Am J Physiol Renal Physiol 2015 308 F377 F387. doi: 10.1152/ajprenal.00477.2013.
118. Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME, Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ Res 2015 116 991 1006. doi: 10.1161/CIRCRESAHA.116.305697.
119. Huby AC, Antonova G, Groenendyk J, Gomez-Sanchez CE, Bollag WB, Filosa JA, Belin de Chantemèle EJ, Adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis. Circulation 2015 132 2134 2145. doi: 10.1161/CIRCULATIONAHA.115.018226.
120. Shibuya I, Utsunomiya K, Toyohira Y, Ueno S, Tsutsui M, Cheah TB, Ueta Y, Izumi F, Yanagihara N, Regulation of catecholamine synthesis by leptin. Ann N Y Acad Sci 2002 971 522 527
121. Penn DM, Jordan LC, Kelso EW, Davenport JE, Harris RB, Effects of central or peripheral leptin administration on norepinephrine turnover in defined fat depots. Am J Physiol Regul Integr Comp Physiol 2006 291 R1613 R1621. doi: 10.1152/ajpregu.00368.2006.
122. Hall JE, Hildebrandt DA, Kuo J, Obesity hypertension: role of leptin and sympathetic nervous system. Am J Hypertens 2001 14 6 Pt 2 103S 115S
123. Bełtowski J, Jamroz-Wiśniewska A, Borkowska E, Wójcicka G, Up-regulation of renal Na+, K+-ATPase: the possible novel mechanism of leptin-induced hypertension. Pol J Pharmacol 2004 56 213 222
124. Jamroz-Wiśniewska A, Wójcicka G, Łowicka E, Ksiazek M, Bełtowski J, Transactivation of epidermal growth factor receptor in vascular and renal systems in rats with experimental hyperleptinemia: role in leptin-induced hypertension. Biochem Pharmacol 2008 75 1623 1638. doi: 10.1016/j.bcp.2008.01.003.
125. Bełtowski J, Jazmroz-Wiśniewska A, Transactivation of ErbB receptors by leptin in the cardiovascular system: mechanisms, consequences and target for therapy. Curr Pharm Des 2014 20 616 624
126. Lim K, Barzel B, Burke SL, Armitage JA, Head GA, Origin of aberrant blood pressure and sympathetic regulation in diet-induced obesity. Hypertension 2016 68 491 500. doi: 10.1161/HYPERTENSIONAHA.116.07461.
127. Flanagan DE, Vaile JC, Petley GW, Phillips DI, Godsland IF, Owens P, Moore VM, Cockington RA, Robinson JS, Gender differences in the relationship between leptin, insulin resistance and the autonomic nervous system. Regul Pept 2007 140 37 42. doi: 10.1016/j.regpep.2006.11.009.
128. Rajapurohitam V, Javadov S, Purdham DM, Kirshenbaum LA, Karmazyn M, An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects of angiotensin II and endothelin-1. J Mol Cell Cardiol 2006 41 265 274. doi: 10.1016/j.yjmcc.2006.05.001.
129. Purdham DM, Rajapurohitam V, Zeidan A, Huang C, Gross GJ, Karmazyn M, A neutralizing leptin receptor antibody mitigates hypertrophy and hemodynamic dysfunction in the postinfarcted rat heart. Am J Physiol Heart Circ Physiol 2008 295 H441 H446. doi: 10.1152/ajpheart.91537.2007.
130. Moro C, Grauzam S, Ormezzano O, Toufektsian MC, Tanguy S, Calabrese P, Coll JL, Bak I, Juhasz B, Tosaki A, de Leiris J, Boucher F, Inhibition of cardiac leptin expression after infarction reduces subsequent dysfunction. J Cell Mol Med 2011 15 1688 1694. doi: 10.1111/j.1582-4934.2010.01154.x.
131. Gutiérrez-Tenorio J, Marín-Royo G, Martínez-Martínez E, Martín R, Miana M, López-Andrés N, Jurado-López R, Gallardo I, Luaces M, San Román JA, González-Amor M, Salaices M, Nieto ML, Cachofeiro V, The role of oxidative stress in the crosstalk between leptin and mineralocorticoid receptor in the cardiac fibrosis associated with obesity. Sci Rep 2017 7 16802. doi: 10.1038/s41598-017-17103-9.
132. Martínez-Martínez E, Jurado-López R, Valero-Muñoz M, Bartolomé MV, Ballesteros S, Luaces M, Briones AM, López-Andrés N, Miana M, Cachofeiro V, Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: potential role in obesity. J Hypertens 2014 32 1104 1114. doi: 10.1097/HJH.0000000000000149.
133. Zibadi S, Cordova F, Slack EH, Watson RR, Larson DF, Leptin's regulation of obesity-induced cardiac extracellular matrix remodeling. Cardiovasc Toxicol 2011 11 325 333. doi: 10.1007/s12012-011-9124-0.
134. Abe Y, Ono K, Kawamura T, Wada H, Kita T, Shimatsu A, Hasegawa K, Leptin induces elongation of cardiac myocytes and causes eccentric left ventricular dilatation with compensation. Am J Physiol Heart Circ Physiol 2007 292 H2387 H2396. doi: 10.1152/ajpheart.00579.2006.
135. Rajapurohitam V, Gan XT, Kirshenbaum LA, Karmazyn M, The obesity-associated peptide leptin induces hypertrophy in neonatal rat ventricular myocytes. Circ Res 2003 93 277 279. doi: 10.1161/01.RES.0000089255.37804.72.
136. Perego L, Pizzocri P, Corradi D, Maisano F, Paganelli M, Fiorina P, Barbieri M, Morabito A, Paolisso G, Folli F, Pontiroli AE, Circulating leptin correlates with left ventricular mass in morbid (grade III) obesity before and after weight loss induced by bariatric surgery: a potential role for leptin in mediating human left ventricular hypertrophy. J Clin Endocrinol Metab 2005 90 4087 4093. doi: 10.1210/jc.2004-1963.
137. Na T, Dai DZ, Tang XY, Dai Y, Upregulation of leptin pathway correlates with abnormal expression of SERCA2a, phospholamban and the endothelin pathway in heart failure and reversal by CPU86017. Naunyn Schmiedebergs Arch Pharmacol 2007 375 39 49. doi: 10.1007/s00210-007-0134-1.
138. Van den Bergh A, Vanderper A, Vangheluwe P, Desjardins F, Nevelsteen I, Verreth W, Wuytack F, Holvoet P, Flameng W, Balligand JL, Herijgers P, Dyslipidaemia in type II diabetic mice does not aggravate contractile impairment but increases ventricular stiffness. Cardiovasc Res 2008 77 371 379. doi: 10.1093/cvr/cvm001.
139. Edelmann F, Tomaschitz A, Wachter R, Gelbrich G, Knoke M, Düngen HD, Pilz S, Binder L, Stahrenberg R, Schmidt A, März W, Pieske B, Serum aldosterone and its relationship to left ventricular structure and geometry in patients with preserved left ventricular ejection fraction. Eur Heart J 2012 33 203 212. doi: 10.1093/eurheartj/ehr292.
140. Martínez-Martínez E, Miana M, Jurado-López R, Bartolomé MV, Souza Neto FV, Salaices M, López-Andrés N, Cachofeiro V, The potential role of leptin in the vascular remodeling associated with obesity. Int J Obes (Lond) 2014 38 1565 1572. doi: 10.1038/ijo.2014.37.
141. Gruzdeva OV, Akbasheva OE, Dyleva YA, Antonova LV, Matveeva VG, Uchasova EG, Fanaskova EV, Karetnikova VN, Ivanov SV, Barbarash OL, Adipokine and cytokine profiles of epicardial and subcutaneous adipose tissue in patients with coronary heart disease. Bull Exp Biol Med 2017 163 608 611. doi: 10.1007/s10517-017-3860-5.
142. Iacobellis G, Diaz S, Mendez A, Goldberg R, Increased epicardial fat and plasma leptin in type 1 diabetes independently of obesity. Nutr Metab Cardiovasc Dis 2014 24 725 729. doi: 10.1016/j.numecd.2013.11.001.
143. Mach L, Bedanova H, Soucek M, Karpisek M, Konecny T, Nemec P, Orban M, Impact of cardiopulmonary bypass surgery on cytokines in epicardial adipose tissue: comparison with subcutaneous fat. Perfusion 2017 32 279 284. doi: 10.1177/0267659116683791.
144. Chang HX, Zhao XJ, Zhu QL, Hou Q, Li Y, Removal of epicardial adipose tissue after myocardial infarction improves cardiac function [published online ahead of print April 4, 2017]. Herz. doi: 10.1007/s00059-017-4555-4.
145. Naftali-Shani N, Itzhaki-Alfia A, Landa-Rouben N, Kain D, Holbova R, Adutler-Lieber S, Molotski N, Asher E, Grupper A, Millet E, Tessone A, Winkler E, Kastrup J, Feinberg MS, Zipori D, Pevsner-Fischer M, Raanani E, Leor J, The origin of human mesenchymal stromal cells dictates their reparative properties. J Am Heart Assoc 2013 2 e000253. doi: 10.1161/JAHA.113.000253.
146. Fukui A, Ikebe-Ebata Y, Kondo H, Saito S, Aoki K, Fukunaga N, Shinohara T, Masaki T, Teshima Y, Takahashi N, Hyperleptinemia exacerbates high-fat diet-mediated atrial fibrosis and fibrillation. J Cardiovasc Electrophysiol 2017 28 702 710. doi: 10.1111/jce.13200.
147. Fukui A, Takahashi N, Nakada C, Masaki T, Kume O, Shinohara T, Teshima Y, Hara M, Saikawa T, Role of leptin signaling in the pathogenesis of angiotensin II-mediated atrial fibrosis and fibrillation. Circ Arrhythm Electrophysiol 2013 6 402 409. doi: 10.1161/CIRCEP.111.000104.
148. Akilli H, Kayrak M, Bekci TT, Erdogan Hİ Aribas A, Yildirim O, Taner A, Erer M, Unlu A, Gender-related changes of the epicardial fat thickness and leptin in obstructive sleep apnea. Echocardiography 2014 31 411 419. doi: 10.1111/echo.12392.
149. Fontes-Carvalho R, Pimenta J, Bettencourt P, Leite-Moreira A, Azevedo A, Association between plasma leptin and adiponectin levels and diastolic function in the general population. Expert Opin Ther Targets 2015 19 1283 1291. doi: 10.1517/14728222.2015.1019468.
150. Meléndez GC, McLarty JL, Levick SP, Du Y, Janicki JS, Brower GL, Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats. Hypertension 2010 56 225 231. doi: 10.1161/HYPERTENSIONAHA.109.148635.
151. Westermann D, Van Linthout S, Dhayat S, Dhayat N, Schmidt A, Noutsias M, Song XY, Spillmann F, Riad A, Schultheiss HP, Tschöpe C, Tumor necrosis factor-alpha antagonism protects from myocardial inflammation and fibrosis in experimental diabetic cardiomyopathy. Basic Res Cardiol 2007 102 500 507. doi: 10.1007/s00395-007-0673-0.
152. Blyszczuk P, Kania G, Dieterle T, Marty RR, Valaperti A, Berthonneche C, Pedrazzini T, Berger CT, Dirnhofer S, Matter CM, Penninger JM, Lüscher TF, Eriksson U, Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy. Circ Res 2009 105 912 920. doi: 10.1161/CIRCRESAHA.109.199802.
153. Hernández-Romero D, Orenes-Piñero E, García-Honrubia A, Climent V, Romero-Aniorte AI, Martínez CM, García-Bautista M, Martínez M, Feliu E, González J, Cánovas S, Montero-Argudo JA, Valdés M, Marín F, Involvement of the-420C>G RETN polymorphism in myocardial fibrosis in patients with hypertrophic cardiomyopathy. J Intern Med 2015 278 50 58. doi: 10.1111/joim.12334.
154. Hofmann U, Heuer S, Meder K, Boehler J, Lange V, Quaschning T, Ertl G, Bonz A, The proinflammatory cytokines TNF-alpha and IL-1 beta impair economy of contraction in human myocardium. Cytokine 2007 39 157 162. doi: 10.1016/j.cyto.2007.07.185.
155. Van Tassell BW, Seropian IM, Toldo S, Mezzaroma E, Abbate A, Interleukin-1β induces a reversible cardiomyopathy in the mouse. Inflamm Res 2013 62 637 640. doi: 10.1007/s00011-013-0625-0.
156. Panagiotakos DB, Pitsavos C, Yannakoulia M, Chrysohoou C, Stefanadis C, The implication of obesity and central fat on markers of chronic inflammation: the ATTICA study. Atherosclerosis 2005 183 308 315. doi: 10.1016/j.atherosclerosis.2005.03.010.
157. Arsenault BJ, Cartier A, Côté M, Lemieux I, Tremblay A, Bouchard C, Pérusse L, Després JP, Body composition, cardiorespiratory fitness, and low-grade inflammation in middle-aged men and women. Am J Cardiol 2009 104 240 246. doi: 10.1016/j.amjcard.2009.03.027.
158. Lisko I, Tiainen K, Stenholm S, Luukkaala T, Hurme M, Lehtimäki T, Hervonen A, Jylhä M. Inflammation, adiposity, and mortality in the oldest old. Rejuvenation Res. 2012;15:445-452. doi: 10.1089/rej.2011.1310.
159. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323:236-241. doi: 10.1056/NEJM199007263230405.
160. Aleksova A, Beltrami A P, Carriere C, Barbati G, Lesizza P, Perrieri-Mon-tanino M, Isola M, Gentile P, Salvioni E, Not T, Agostoni P, Sinagra G. Interleukin-1β levels predict long-term mortality and need for heart transplantation in ambulatory patients affected by idiopathic dilated cardio-myopathy. Oncotarget. 2017;8:25131-25140. doi: 10.18632/oncotar-get.15349.
161. Frankel DS, Vasan RS, D'Agostino RB Sr, Benjamin EJ, Levy D, Wang TJ, Meigs JB. Resistin, adiponectin, and risk of heart failure the Fram-ingham offspring study. J Am Coll Cardiol. 2009;53:754-762. doi: 10.1016/j.jacc.2008.07.073.
162. Maeda K, Tsutamoto T, Wada A, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T, Kinoshita M. High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure. J Am Coll Cardiol. 2000;36:1587-1593.
163. Testa M, Yeh M, Lee P, Fanelli R, Loperfdo F, Berman JW, LeJemtel TH. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol. 1996;28:964-971.
164. Lee DL, Sturgis LC, Labazi H, Osborne JB Jr, Fleming C, Pollock JS, Man-hiani M, Imig JD, Brands MW. Angiotensin II hypertension is attenuated in interleukin-6 knockout mice. Am J Physiol Heart Circ Physiol. 2006;290:H935-H940. doi: 10.1152/ajpheart.00708.2005.
165. Nakamura A, Kohsaka T, Johns EJ. Differential regulation of interleukin-6 production in the kidney by the renal sympathetic nerves in normal and spontaneously hypertensive rats. J Hypertens. 1993;11:491-497.
166. Habeeballah H, Alsuhaymi N, Stebbing MJ, Badoer E. Effects of central administration of resistin on renal sympathetic nerve activity in rats fed a high-fat diet: a comparison with leptin. J Neuroendocrinol. 2017;29. doi: 10.1111/jne.12495.
167. Kirchgessner TG, Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Tumor necrosis factor-alpha contributes to obesity-related hyper-leptinemia by regulating leptin release from adipocytes. J Clin Invest. 1997;100:2777-2782. doi: 10.1172/JCI119824.
168. Natarajan R, Ploszaj S, Horton R, Nadler J. Tumor necrosis factor and interleukin-1 are potent inhibitors of angiotensin-II-induced al-dosterone synthesis. Endocrinology. 1989;125:3084-3089. doi: 10.1210/endo-125-6-3084.
169. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT; Anti-TNF Therapy Against Congestive Heart Failure Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infiximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107:3133-3140. doi: 10.1161/01.CIR.0000077913.60364.D2.
170. Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, Djian J, Drexler H, Feldman A, Kober L, Krum H, Liu P, Nieminen M, Tavazzi L, van Veldhuisen DJ, Waldenstrom A, Warren M, Westheim A, Zannad F, Fleming T. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation. 2004;109:1594-1602. doi: 10.1161/01.CIR.0000124490.27666.B2.
171. Van Tassell BW, Abouzaki NA, Oddi Erdle C, Carbone S, Trankle CR, Melchior RD, Turlington JS, Thurber CJ, Christopher S, Dixon DL, Fronk DT, Thomas CS, Rose SW, Buckley LF, Dinarello CA, Biondi-Zoccai G, Abbate A. Interleukin-1 blockade in acute decompen-sated heart failure: a randomized, double-blinded, placebo-controlled pilot study. J Cardiovasc Pharmacol. 2016;67:544-551. doi: 10.1097/FJC.0000000000000378.
172. Johns DG, Duffy J, Fisher T, Hubbard BK, Forrest MJ. On-and off-target pharmacology of torcetrapib: current understanding and implications for the structure activity relationships (SAR), discovery and development of cholesteryl ester-transfer protein (CETP) inhibitors. Drugs. 2012;72:491-507. doi: 10.2165/11599310-000000000-00000.
173. Amin RH, Mathews ST, Alli A, Leff T. Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPARgamma-dependent autocrine mechanism. Am J Physiol Heart Circ Physiol. 2010;299:H690-H698. doi: 10.1152/ajpheart.01032.2009.
174. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, Kumada M, Sato K, Schiekofer S, Ohashi K, Funahashi T, Colucci WS, Walsh K. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004;10:1384-1389. doi: 10.1038/nm1137.
175. Qi GM, Jia LX, Li YL, Li HH, Du J. Adiponectin suppresses angioten-sin II-induced infammation and cardiac fbrosis through activation of macrophage autophagy. Endocrinology. 2014;155:2254-2265. doi: 10.1210/en.2013-2011.
176. Afzal S, Sattar MA, Johns EJ, Abdulla MH, Akhtar S, Hashmi F, Abdullah NA. Interaction between irbesartan, peroxisome proliferator-activated receptor (PPAR-γ), and adiponectin in the regulation of blood pressure and renal function in spontaneously hypertensive rats. J Physiol Biochem. 2016;72:593-604. doi: 10.1007/s13105-016-0497-1.
177. Bussey CT, Kolka CM, Rattigan S, Richards SM. Adiponectin opposes endothelin-1-mediated vasoconstriction in the perfused rat hindlimb. Am J Physiol Heart Circ Physiol. 2011;301:H79-H86. doi: 10.1152/ajpheart.00864.2010.
178. Tanida M, Shen J, Horii Y, Matsuda M, Kihara S, Funahashi T, Shimomura I, Sawai H, Fukuda Y, Matsuzawa Y, Nagai K. Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats. Exp Biol Med (Maywood). 2007;232:390-397.
179. Huang H, Han Y, Jose PA, Zeng C. Loss of adiponectin-induced renal sodium excretion in hypertension. J Am Soc Hypertens. 2016 Jul;10(Suppl 1):e4. doi: 10.1016/j.jash.2016.06.013.
180. Li P, Sun F, Cao HM, Ma QY, Pan CM, Ma JH, Zhang XN, Jiang H, Song HD, Chen MD. Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates ste-roidogenesis. Biochem Biophys Res Commun. 2009;390:1208-1213. doi: 10.1016/j.bbrc.2009.10.122.
181. Wang LL, Miller D, Wanders D, Nanayakkara G, Amin R, Judd R, Morrison EE, Zhong JM. Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats. Acta Pharmacol Sin. 2016;37:187-195. doi: 10.1038/aps.2015.84.
182. O'Shea KM, Chess DJ, Khairallah RJ, Rastogi S, Hecker PA, Sabbah HN, Walsh K, Stanley WC. Effects of adiponectin defciency on struc-tural and metabolic remodeling in mice subjected to pressure overload. Am J Physiol Heart Circ Physiol. 2010;298:H1639-H1645. doi: 10.1152/ajpheart.00957.2009.
183. Essick EE, Ouchi N, Wilson RM, Ohashi K, Ghobrial J, Shibata R, Pimen-tel DR, Sam F. Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling. Am J Physiol Heart Circ Physiol. 2011;301:H984-H993. doi: 10.1152/ajpheart.00428.2011.
184. Shibata R, Izumiya Y, Sato K, Papanicolaou K, Kihara S, Colucci WS, Sam F, Ouchi N, Walsh K. Adiponectin protects against the development of systolic dysfunction following myocardial infarction. J Mol Cell Cardiol. 2007;42:1065-1074. doi: 10.1016/j.yjmcc.2007.03.808.
185. Degawa-Yamauchi M, Moss KA, Bovenkerk JE, Shankar SS, Morrison CL, Lel-liott CJ, Vidal-Puig A, Jones R, Considine R V. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor alpha. Obes Res. 2005;13:662-669. doi: 10.1038/oby.2005.74.
186. Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G. Adiponec-tin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes. 2003;52:1779-1785.
187. Simons PJ, van den Pangaart PS, Aerts JM, Boon L. Pro-infammatory delipidizing cytokines reduce adiponectin secretion from human adi-pocytes without affecting adiponectin oligomerization. J Endocrinol. 2007;192:289-299. doi: 10.1677/JOE-06-0047.
188. Li P, Zhang XN, Pan CM, Sun F, Zhu DL, Song HD, Chen MD. Aldosterone perturbs adiponectin and PAI-1 expression and secretion in 3T3-L1 adipo-cytes. Horm Metab Res. 2011;43:464-469. doi: 10.1055/s-0031-1277226.
189. Yuan G, Jia J, Di L, Zhou L, Dong S, Ye J, Wang D, Yang L, Wang J, Li L, Yang Y, Mao C, Chen M. Effects of C-reactive protein on adipokines genes expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2012;424:462-468. doi: 10.1016/j.bbrc.2012.06.133.
190. Gao C, Liu Y, Yu Q, Yang Q, Li B, Sun L, Yan W, Cai X, Gao E, Xiong L, Wang H, Tao L. TNF-α antagonism ameliorates myocardial ischemia-reper-fusion injury in mice by upregulating adiponectin. Am J Physiol Heart Circ Physiol. 2015;308:H1583-H1591. doi: 10.1152/ajpheart.00346.2014.
191. Chazenbalk G, Trivax BS, Yildiz BO, Bertolotto C, Mathur R, Heneidi S, Azziz R. Regulation of adiponectin secretion by adipocytes in the polycys-tic ovary syndrome: role of tumor necrosis factor-{alpha}. J Clin Endocrinol Metab. 2010;95:935-942. doi: 10.1210/jc.2009-1158.
192. Kistorp C, Faber J, Galatius S, Gustafsson F, Frystyk J, Flyvbjerg A, Hil-debrandt P. Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation. 2005;112:1756-1762. doi: 10.1161/CIRCULATIONAHA.104.530972.
193. Christensen HM, Schou M, Goetze J P, Faber J, Frystyk J, Flyvbjerg A, Kistorp C. Body mass index in chronic heart failure: association with biomarkers of neurohormonal activation, infammation and endothelial dysfunction. BMC Cardiovasc Disord. 2013;13:80. doi: 10.1186/1471-2261-13-80.
194. Takiguchi M, Yoshihisa A, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Iwaya S, Owada T, Miyata M, Abe S, Sato T, Suzuki S, Suzuki H, Saitoh S, Takeishi Y. Impact of body mass index on mortality in heart failure patients. Eur J Clin Invest. 2014;44:1197-1205. doi: 10.1111/eci.12354.
195. Norvik JV, Schirmer H, Ytrehus K, Jenssen TG, Zykova SN, Eggen AE, Er-iksen BO, Solbu MD. Low adiponectin is associated with diastolic dysfunction in women: a cross-sectional study from the Tromsø Study. BMC Cardiovasc Disord. 2017;17:79. doi: 10.1186/s12872-017-0509-2.
196. Ybarra J, Resmini E, Planas F, Navarro-López F, Webb S, Pou JM, Santos A, Ballesta-López C. Relationship between adiponectin and left atrium size in uncomplicated obese patients: adiponectin, a link between fat and heart. Obes Surg. 2009;19:1324-1332. doi: 10.1007/s11695-009-9924-5.
197. Shaver A, Nichols A, Thompson E, Mallick A, Payne K, Jones C, Manne ND, Sundaram S, Shapiro JI, Sodhi K. Role of serum biomarkers in early detection of diabetic cardiomyopathy in the West Virginian population. Int J Med Sci. 2016;13:161-168. doi: 10.7150/ijms.14141.
198. Fu M, Zhou J, Qian J, Jin X, Zhu H, Zhong C, Fu M, Zou Y, Ge J. Adiponec-tin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction: an experimental study. Lipids Health Dis. 2012;11:106. doi: 10.1186/1476-511X-11-106.
199. Beatty AL, Zhang MH, Ku IA, Na B, Schiller NB, Whooley MA. Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study. Atherosclerosis. 2012;220:587-592. doi: 10.1016/j.atherosclerosis.2011.11.038.
200. Liao Y, Takashima S, Maeda N, Ouchi N, Komamura K, Shimomura I, Hori M, Matsuzawa Y, Funahashi T, Kitakaze M. Exacerbation of heart failure in adiponectin-defcient mice due to impaired regulation of AMPK and glucose metabolism. Cardiovasc Res. 2005;67:705-713. doi: 10.1016/j.cardiores.2005.04.018.
201. Tanaka K, Wilson RM, Essick EE, Duffen JL, Scherer PE, Ouchi N, Sam F. Effects of adiponectin on calcium-handling proteins in heart failure with preserved ejection fraction. Circ Heart Fail. 2014;7:976-985. doi: 10.1161/CIRCHEARTFAILURE.114.001279.
202. Sam F, Duhaney TA, Sato K, Wilson RM, Ohashi K, Sono-Romanelli S, Higuchi A, De Silva DS, Qin F, Walsh K, Ouchi N. Adiponectin def-ciency, diastolic dysfunction, and diastolic heart failure. Endocrinology. 2010;151:322-331. doi: 10.1210/en.2009-0806.
203. Yi W, Sun Y, Gao E, Wei X, Lau WB, Zheng Q, Wang Y, Yuan Y, Wang X, Tao L, Li R, Koch W, Ma XL. Reduced cardioprotective action of adi-ponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms. Antioxid Redox Signal. 2011;15:1779-1788. doi: 10.1089/ars.2010.3722.
204. Li R, Xu M, Wang X, Wang Y, Lau WB, Yuan Y, Yi W, Wei X, Lopez BL, Christopher TA, Wang XM, Ma XL. Reduced vascular responsiveness to adiponectin in hyperlipidemic rats: mechanisms and signifcance. J Mol Cell Cardiol. 2010;49:508-515. doi: 10.1016/j.yjmcc.2010.03.002.
205. Engin A. Adiponectin-resistance in obesity. Adv Exp Med Biol. 2017;960:415-441. doi: 10.1007/978-3-319-48382-5-18.
206. Skurk C, Wittchen F, Suckau L, Witt H, Noutsias M, Fechner H, Schultheiss H P, Poller W. Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy. Eur Heart J. 2008;29:1168-1180. doi: 10.1093/eurheartj/ehn136.
207. Giannessi D, Caselli C, Del Ry S, Maltinti M, Pardini S, Turchi S, Cabiati M, Sampietro T, Abraham N, L'abbate A, Neglia D. Adiponectin is associated with abnormal lipid profle and coronary microvascular dysfunction in patients with dilated cardiomyopathy without overt heart failure. Metabolism. 2011;60:227-233. doi: 10.1016/j.metabol.2009.12.030.
208. Caselli C, Lionetti V, Cabiati M, Prescimone T, Aquaro GD, Ottaviano V, Bernini F, Mattii L, Del Ry S, Giannessi D. Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model. Cardiovasc Diabetol. 2012;11:143. doi: 10.1186/1475-2840-11-143.
209. Takano H, Obata JE, Kodama Y, Kitta Y, Nakamura T, Mende A, Kawabata K, Saito Y, Fujioka D, Kobayashi T, Yano T, Sano K, Kugiyama K. Adiponec-tin is released from the heart in patients with heart failure. Int J Cardiol. 2009;132:221-226. doi: 10.1016/j.ijcard.2007.11.040.
210. Szabó T, Scherbakov N, Sandek A, Kung T, von Haehling S, Lainscak M, Jankowska EA, Rudovich N, Anker SD, Frystyk J, Flyvbjerg A, Pfei-ffer A F, Doehner W. Plasma adiponectin in heart failure with and without cachexia: catabolic signal linking catabolism, symptomatic sta-tus, and prognosis. Nutr Metab Cardiovasc Dis. 2014;24:50-56. doi: 10.1016/j.numecd.2013.04.015.
211. George J, Patal S, Wexler D, Sharabi Y, Peleg E, Kamari Y, Grossman E, Sheps D, Keren G, Roth A. Circulating adiponectin concentrations in patients with congestive heart failure. Heart. 2006;92:1420-1424. doi: 10.1136/hrt.2005.083345.
212. Loncar G, Bozic B, von Haehling S, Düngen HD, Prodanovic N, Lainscak M, Arandjelovic A, Dimkovic S, Radojicic Z, Popovic V. Association of adipo-nectin with peripheral muscle status in elderly patients with heart failure. Eur J Intern Med. 2013;24:818-823. doi: 10.1016/j.ejim.2013.09.011.
213. McEntegart MB, Awede B, Petrie MC, Sattar N, Dunn FG, MacFarlane NG, McMurray JJ. Increase in serum adiponectin concentration in pa-tients with heart failure and cachexia: relationship with leptin, other cyto-kines, and B-type natriuretic peptide. Eur Heart J. 2007;28:829-835. doi: 10.1093/eurheartj/ehm033.
214. Yu H P, Jen HL, Yin WH, Wei J. Circulating adiponectin levels following treatment can predict late clinical outcomes in chronic heart failure. Acta Cardiol Sin. 2017;33:139-149.
215. Matsumoto M, Lee-Kawabata M, Tsujino T, Naito Y, Ezumi A, Sakoda T, Ohyanagi M, Shimomura I, Masuyama T. Decrease in serum adiponectin levels in response to treatment predicts good prognosis in acute decom-pensated heart failure. J Clin Hypertens (Greenwich). 2010;12:900-904. doi: 10.1111/j.1751-7176.2010.00368.x.
216. Haugen E, Furukawa Y, Isic A, Fu M. Increased adiponectin level in parallel with increased NT-pro BNP in patients with severe heart failure in the elderly: a hospital cohort study. Int J Cardiol. 2008;125:216-219. doi: 10.1016/j.ijcard.2007.12.002.
217. Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A, Okazaki H, Asai M, Nagamachi Y, Maeda N, Shintani Y, Minamino T, Asakura M, Kishimoto I, Funahashi T, Tomoike H, Kitakaze M. Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol. 2009;53:2070-2077. doi: 10.1016/j.jacc.2009.02.038.
218. Tanaka T, Tsutamoto T, Sakai H, Nishiyama K, Fujii M, Yamamoto T, Horie M. Effect of atrial natriuretic peptide on adiponectin in patients with heart failure. Eur J Heart Fail. 2008;10:360-366. doi: 10.1016/j.ejheart.2008.02.005.
219. Antonopoulos AS, Margaritis M, Coutinho P, Digby J, Patel R, Psarros C, Ntusi N, Karamitsos TD, Lee R, De Silva R, Petrou M, Sayeed R, Dem-osthenous M, Bakogiannis C, Wordsworth PB, Tousoulis D, Neubauer S, Channon KM, Antoniades C. Reciprocal effects of systemic infammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol. 2014;34:2151-2159. doi: 10.1161/ATVBAHA.114.303828.
220. Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Martinet W, Van Hoof V, Vrints CJ, Ventura-Clapier R, Conraads VM. Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure. Circ Heart Fail. 2010;3:185-194. doi: 10.1161/CIRCHEARTFAILURE.109.885525.
221. Miura S, Nakayama A, Tomita S, Matsuo Y, Suematsu Y, Saku K. Comparison of aldosterone synthesis in adrenal cells, effect of various AT1 receptor blockers with or without atrial natriuretic peptide. Clin Exp Hypertens. 2015;37:353-357. doi: 10.3109/10641963.2014.987391.
222. Miura SI, Suematsu Y, Matsuo Y, Tomita S, Nakayama A, Goto M, Arimura T, Kuwano T, Yahiro E, Saku K. The angiotensin II type 1 receptor-neprilysin inhibitor LCZ696 blocked aldosterone synthesis in a human adrenocortical cell line. Hypertens Res. 2016;39:758-763. doi: 10.1038/hr.2016.72.
223. Martin FL, Stevens TL, Cataliotti A, Schirger JA, Borgeson DD, Redfeld MM, Luchner A, Burnett JC Jr. Natriuretic and antialdosterone actions of chronic oral NEP inhibition during progressive congestive heart failure. Kidney Int. 2005;67:1723-1730. doi: 10.1111/j.1523-1755.2005.00269.x.
224. von Lueder TG, Wang BH, Kompa AR, Huang L, Webb R, Jordaan P, Atar D, Krum H. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fbrosis and hypertrophy. Circ Heart Fail. 2015;8:71-78. doi: 10.1161/CIRCHEARTFAILURE.114.001785.
225. Pu Q, Amiri F, Gannon P, Schiffrin EL. Dual angiotensin-converting enzyme/neutral endopeptidase inhibition on cardiac and renal fbro-sis and infammation in DOCA-salt hypertensive rats. J Hypertens. 2005;23:401-409.
226. Bayés-Genís A, Barallat J, Galán A, de Antonio M, Domingo M, Zamora E, Urrutia A, Lupón J. Soluble neprilysin is predictive of cardiovascular death and heart failure hospitalization in heart failure patients. J Am Coll Cardiol. 2015;65:657-665. doi: 10.1016/j.jacc.2014.11.048.
227. Núñez J, Núñez E, Barallat J, Bodí V, Miñana G, Pastor MC, Sanchis J, Lupón J, Bayes-Genis A. Serum neprilysin and recurrent admissions in patients with heart failure. J Am Heart Assoc. 2017;6. pii: e005712. doi: 10.1161/JAHA.117.005712.
228. Bayés-Genís A, Barallat J, Pascual-Figal D, Pascual D, Nuñez J, Miñana G, Sánchez-Mas J, Galan A, Sanchis J, Zamora E, Pérez-Martínez MT, Lupón J. Prognostic value and kinetics of soluble neprilysin in acute heart failure: a pilot study. JACC Heart Fail. 2015;3:641-644. doi: 10.1016/j.jchf.2015.03.006.
229. Maki T, Nasa Y, Tanonaka K, Takahashi M, Takeo S. Direct inhibition of neutral endopeptidase in vasopeptidase inhibitor-mediated amelioration of cardiac remodeling in rats with chronic heart failure. Mol Cell Biochem. 2003;254:265-273.
230. Bäcklund T, Palojoki E, Saraste A, Grönholm T, Eriksson A, Lakkisto P, Vuolteenaho O, Nieminen MS, Voipio-Pulkki LM, Laine M, Tikkanen I. Effect of vasopeptidase inhibitor omapatrilat on cardiomyocyte apoptosis and ventricular remodeling in rat myocardial infarction. Cardiovasc Res. 2003;57:727-737.
231. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. doi: 10.1056/NEJMoa1409077.
232. Schling P, Schäfer T. Human adipose tissue cells keep tight control on the angiotensin II levels in their vicinity. J Biol Chem. 2002;277:48066-48075. doi: 10.1074/jbc.M204058200.
233. Ong WK, Tan CS, Chan KL, Goesantoso GG, Chan XH, Chan E, Yin J, Yeo CR, Khoo CM, So JB, Shabbir A, Toh SA, Han W, Sugii S. Identifcation of specifc cell-surface markers of adipose-derived stem cells from subcutaneous and visceral fat depots. Stem Cell Reports. 2014;2:171-179. doi: 10.1016/j.stemcr.2014.01.002.
234. Standeven KF, Hess K, Carter AM, Rice GI, Cordell PA, Balmforth AJ, Lu B, Scott DJ, Turner AJ, Hooper NM, Grant PJ. Neprilysin, obesity and the metabolic syndrome. Int J Obes (Lond). 2011;35:1031-1040. doi: 10.1038/ijo.2010.227.
235. Rice GI, Jones AL, Grant PJ, Carter AM, Turner AJ, Hooper NM. Circulating activities of angiotensin-converting enzyme, its homolog, angioten-sin-converting enzyme 2, and neprilysin in a family study. Hypertension. 2006;48:914-920. doi: 10.1161/01.HYP.0000244543.91937.79.
236. Goliasch G, Pavo N, Zotter-Tufaro C, Kammerlander A, Duca F, Mascherbauer J, Bonderman D. Soluble neprilysin does not correlate with outcome in heart failure with preserved ejection fraction. Eur J Heart Fail. 2016;18:89-93. doi: 10.1002/ejhf.435.
237. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW, Vasan RS. Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004;109:594-600. doi: 10.1161/01.CIR.0000112582.16683.EA.
238. Lanfear DE, Chow S, Padhukasahasram B, Li J, Langholz D, Tang WH, Williams LK, Sabbah HN. Genetic and nongenetic factors infuencing phar-macokinetics of B-type natriuretic peptide. J Card Fail. 2014;20:662-668. doi: 10.1016/j.cardfail.2014.06.357.
239. St Peter JV, Hartley GG, Murakami MM, Apple FS. B-type natriuretic pep-tide (BNP) and N-terminal pro-BNP in obese patients without heart failure: relationship to body mass index and gastric bypass surgery. Clin Chem. 2006;52:680-685. doi: 10.1373/clinchem.2005.062562.
240. Maeder MT, Rickenbacher P, Rickli H, Abbühl H, Gutmann M, Erne P, Vuil-liomenet A, Peter M, Pfsterer M, Brunner-La Rocca HP; TIME-CHF Investigators. N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: fndings from the Trial of Intensifed versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF). Eur J Heart Fail. 2013;15:1148-1156. doi: 10.1093/eurjhf/hft076.
241. Khalid U, Wruck LM, Quibrera PM, Bozkurt B, Nambi V, Virani SS, Jneid H, Agarwal S, Chang P P, Loehr L, Basra SS, Rosamond W, Ballantyne CM, Deswal A. BNP and obesity in acute decompensated heart failure with preserved vs. reduced ejection fraction: the Atherosclerosis Risk in Communities Surveillance study. Int J Cardiol. 2017;233:61-66. doi: 10.1016/j.ijcard.2017.01.130.
242. Nadruz W Jr, Claggett BL, McMurray JJ, Packer M, Zile MR, Rouleau JL, Desai AS, Swedberg K, Lefkowitz M, Shi VC, Prescott MF, Solomon SD. Impact of body mass index on the accuracy of N-terminal pro-brain natriuretic peptide and brain natriuretic peptide for predicting outcomes in patients with chronic heart failure and reduced ejection fraction: insights from the PARADIGM-HF study (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial). Circulation. 2016;134:1785-1787. doi: 10.1161/CIRCULATIONAHA.116.024976.
243. Changchien EM, Ahmed S, Betti F, Higa J, Kiely K, Hernandez-Boussard T, Morton J. B-type natriuretic peptide increases after gastric bypass surgery and correlates with weight loss. Surg Endosc. 2011;25:2338-2343. doi: 10.1007/s00464-010-1565-1.
244. Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, Shi V, Bransford T, Takeuchi M, Gong J, Lefkowitz M, Packer M, McMurray JJ; Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) Investigators. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012;380:1387-1395. doi: 10.1016/S0140-6736(12)61227-6.
245. Sengenes C, Stich V, Berlan M, Hejnova J, Lafontan M, Pariskova Z, Galitz-ky J. Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women. Int J Obes Relat Metab Disord. 2002;26:24-32. doi: 10.1038/sj.ijo.0801845.
246. Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessì-Fulgheri P, Zhang C, Taka-hashi N, Sarzani R, Collins S. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adi-pocytes. J Clin Invest. 2012;122:1022-1036. doi: 10.1172/JCI59701.
247. Kim J, Han D, Byun SH, Kwon M, Cho SJ, Koh YH, Yoon K. Neprilysin facilitates adipogenesis through potentiation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Mol Cell Biochem. 2017;430:1-9. doi: 10.1007/s11010-017-2948-6.
248. Achike FI, To NH, Wang H, Kwan CY. Obesity, metabolic syndrome, adi-pocytes and vascular function: a holistic viewpoint. Clin Exp Pharmacol Physiol. 2011;38:1-10. doi: 10.1111/j.1440-1681.2010.05460.x.
249. Blundell JE, Goodson S, Halford JC. Regulation of appetite: role of leptin in signalling systems for drive and satiety. Int J Obes Relat Metab Disord. 2001;25(Suppl 1):S29-S34. doi: 10.1038/sj.ijo.0801693.
250. Vila G, Grimm G, Resl M, Heinisch B, Einwallner E, Esterbauer H, Dieplinger B, Mueller T, Luger A, Clodi M. B-type natriuretic peptide modulates ghre-lin, hunger, and satiety in healthy men. Diabetes. 2012;61:2592-2596. doi: 10.2337/db11-1466.
251. Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M, Kasa-hara M, Hashimoto R, Katsuura G, Mukoyama M, Itoh H, Saito Y, Tanaka I, Otani H, Katsuki M. Cardiac fbrosis in mice lacking brain na-triuretic peptide. Proc Natl Acad Sci USA. 2000;97:4239-4244. doi: 10.1073/pnas.070371497.
252. George I, Morrow B, Xu K, Yi GH, Holmes J, Wu EX, Li Z, Protter AA, Oz MC, Wang J. Prolonged effects of B-type natriuretic peptide infusion on cardiac remodeling after sustained myocardial injury. Am J Physiol Heart Circ Physiol. 2009;297:H708-H717. doi: 10.1152/ajpheart.00661.2008.
253. Fain JN, Kanu A, Bahouth SW, Cowan GS, Lloyd Hiler M. Inhibition of leptin release by atrial natriuretic peptide (ANP) in human adipocytes. Bio-chem Pharmacol. 2003;65:1883-1888.
254. Lane ML, Vesely DL. Reduction of leptin levels by four cardiac hormones: Implications for hypertension in obesity. Exp Ther Med. 2013;6:611-615. doi: 10.3892/etm.2013.1173.
255. Beltowski J, Jamroz-Wisniewska A, Borkowska E, Marciniak A. Phos-phodiesterase 5 inhibitor ameliorates renal resistance to atrial natriuretic peptide associated with obesity and hyperleptinemia. Arch Med Res. 2006;37:307-315. doi: 10.1016/j.arcmed.2005.06.008.
256. Mascareno E, Beckles D, Dhar-Mascareno M, Siddiqui MA. Enhanced hypertrophy in ob/ob mice due to an impairment in expression of atrial natriuretic peptide. Vascul Pharmacol. 2009;51:198-204. doi: 10.1016/j.vph.2009.06.005.
257. Yuan K, Yu J, Shah A, Gao S, Kim SY, Kim SZ, Park BH, Kim SH. Leptin reduces plasma ANP level via nitric oxide-dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1007-R1016. doi: 10.1152/ajpregu.00598.2009.
258. Plante E, Menaouar A, Danalache BA, Broderick TL, Jankowski M, Gut-kowska J. Treatment with brain natriuretic peptide prevents the development of cardiac dysfunction in obese diabetic db/db mice. Diabetologia. 2014;57:1257-1267. doi: 10.1007/s00125-014-3201-4.
259. Richards AM, Wittert GA, Crozier IG, Espiner EA, Yandle TG, Ikram H, Frampton C. Chronic inhibition of endopeptidase 24.11 in essential hypertension: evidence for enhanced atrial natriuretic peptide and angioten-sin II. J Hypertens. 1993;11:407-416.
260. Niedowicz DM, Reeves VL, Platt TL, Kohler K, Beckett TL, Powell DK, Lee TL, Sexton TR, Song ES, Brewer LD, Latimer CS, Kraner SD, Larson KL, Ozcan S, Norris CM, Hersh LB, Porter NM, Wilcock DM, Murphy M P. Obesity and diabetes cause cognitive dysfunction in the absence of accelerated β-amyloid deposition in a novel murine model of mixed or vascular dementia. Acta Neuropathol Commun. 2014;2:64. doi: 10.1186/2051-5960-2-64.
261. Yamamoto N, Tanida M, Ono Y, Kasahara R, Fujii Y, Ohora K, Suzuki K, Sobue K. Leptin inhibits amyloid β-protein degradation through decrease of neprilysin expression in primary cultured astrocytes. Biochem Biophys Res Commun. 2014;445:214-217. doi: 10.1016/j.bbrc.2014.01.168.
262. Walther T, Albrecht D, Becker M, Schubert M, Kouznetsova E, Wiesner B, Maul B, Schliebs R, Grecksch G, Furkert J, Sterner-Kock A, Schultheiss H P, Becker A, Siems WE. Improved learning and memory in aged mice defcient in amyloid beta-degrading neutral endopeptidase. PLoS One. 2009;4:e4590. doi: 10.1371/journal.pone.0004590.
263. Iacobellis G. Local and systemic effects of the multifaceted epicar-dial adipose tissue depot. Nat Rev Endocrinol. 2015;11:363-371. doi: 10.1038/nrendo.2015.58.
264. Sacks HS, Fain JN, Bahouth SW, Ojha S, Frontini A, Budge H, Cinti S, Sy-monds ME. Adult epicardial fat exhibits beige features. J Clin Endocrinol Metab. 2013;98:E1448-E1455. doi: 10.1210/jc.2013-1265
265. Pérez-Belmonte LM, Moreno-Santos I, Gómez-Doblas JJ, García-Pinilla JM, Morcillo-Hidalgo L, Garrido-Sánchez L, Santiago-Fernández C, Crespo-Leiro MG, Carrasco-Chinchilla F, Sánchez-Fernández PL, de Teresa-Galván E, Jiménez-Navarro M. Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure. Int J Med Sci. 2017;14:891-895. doi: 10.7150/ijms.19854
266. Iacobellis G, Barbaro G. The double role of epicardial adipose tissue as pro-and anti-infammatory organ. Horm Metab Res. 2008;40:442-445 doi: 10.1055/s-2008-1062724
267. Ogorodnikova AD, Khan UI, McGinn AP, Zeb I, Budoff MJ, Harman SM, Miller VM, Brinton EA, Manson JE, Hodis HN, Merriam GR, Cedars MI, Taylor HS, Naftolin F, Lobo RA, Santoro N, Wildman RP. Ectopic fat and adipo-kines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study. Obesity (Silver Spring). 2013;21:1726-1733 doi: 10.1002/oby.20200
268. Zdychova J, Kralova Lesna I, Maluskova J, Janousek L, Cahova M, Ka-zdova L. Comparison of gene expression of epicardial and visceral adipocytes with regard to the differentiation stage. Neuro Endocrinol Lett 2012;33(suppl 2):93-97
269. Börekçi A, Gür M, Özaltun B, Baykan AO, Harbalioglu H, Seker T, Sen Ö, Acele A, Gözükara MY, Kuloglu O, Koç M, Çayli M. Epicardial fat thickness in stable coronary artery disease: its relationship with high-sensitive cardiac troponin T and N-terminal pro-brain natriuretic peptide. Coron Artery Dis. 2014;25:685-690. doi: 10.1097/MCA.0000000000000140
270. Bakkum MJ, Danad I, Romijn MA, Stuijfzand WJ, Leonora RM, Tulevski II, Somsen GA, Lammertsma AA, van Kuijk C, van Rossum AC, Raijmak-ers PG, Knaapen P. The impact of obesity on the relationship between epicardial adipose tissue, left ventricular mass and coronary microvascular function. Eur J Nucl Med Mol Imaging. 2015;42:1562-1573. doi: 10.1007/s00259-015-3087-5
271. Gormez S, Demirkan A, Atalar F, Caynak B, Erdim R, Sozer V, Gunay D, Akpinar B, Ozbek U, Buyukdevrim AS. Adipose tissue gene expression of adiponectin, tumor necrosis factor-a and leptin in metabolic syndrome patients with coronary artery disease. Intern Med. 2011;50:805-810
272. Lai YH, Yun CH, Yang FS, Liu CC, Wu YJ, Kuo JY, Yeh HI, Lin TY, Be-zerra HG, Shih SC, Tsai CH, Hung CL. Epicardial adipose tissue relat-ng to anthropometrics, metabolic derangements and fatty liver disease independently contributes to serum high-sensitivity C-reactive protein beyond body fat composition: a study validated with computed tomography. J Am Soc Echocardiogr. 2012;25:234-241. doi: 10.1016/j.echo.2011.09.018.
273. Iacobellis G, Assael F, Ribaudo MC, Zappaterreno A, Alessi G, Di Mario U, Leonetti F. Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction. Obes Res. 2003;11:304-310. doi 10.1038/oby.2003.45
274. Melenovsky V, Borlaug BA, Rosen B, Hay I, Ferruci L, Morell CH, Lakat-ta EG, Najjar SS, Kass DA. Cardiovascular features of heart failure with preserved ejection fraction versus nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore community: the role of atrial remodeling/dysfunction. J Am Coll Cardiol. 2007;49:198-207. doi 10.1016/j.jacc.2006.08.050
275. Karadag B, Ozulu B, Ozturk FY, Oztekin E, Sener N, Altuntas Y. Comparison of epicardial adipose tissue (EAT) thickness and anthropometric measurements in metabolic syndrome (MS) cases above and under the age of 65. Arch Gerontol Geriatr. 2011;52:e79-e84. doi 10.1016/j.archger.2010.06.016
276. Silaghi A, Piercecchi-Marti MD, Grino M, Leonetti G, Alessi MC, Clement K, Dadoun F, Dutour A. Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy Obesity (Silver Spring) 2008;16:2424-2430. doi: 10.1038/oby.2008.379
277. Kalogeropoulos A, Georgiopoulou V, Psaty BM, Rodondi N, Smith AL, Harrison DG, Liu Y, Hoffmann U, Bauer DC, Newman AB, Kritchevsky SB, Harris TB, Butler J; Health ABC Study Investigators. Infammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study. J Am Coll Cardiol. 2010;55:2129-2137 doi: 10.1016/j.jacc.2009.12.045
278. Turak O, Özcan F, Canpolat U, Ijleyen A, Cebeci M, Öksüz F, Mendi MA, Çagli K, Gölba§i Z, Aydogdu S. Increased echocardiographic epicardial fat thickness and high-sensitivity CRP level indicate diastolic dysfunction in patients with newly diagnosed essential hypertension. Blood Press Monit 2013;18:259-264. doi: 10.1097/MBP.0b013e3283651d19
279. Watanabe K, Kishino T, Sano J, Ariga T, Okuyama S, Mori H, Matsushima S, Ohtsuka K, Ohnishi H, Watanabe T. Relationship between epicardial adipose tissue thickness and early impairment of left ventricular systolic function in patients with preserved ejection fraction. Heart Vessels. 2016;31:1010-1015. doi: 10.1007/s00380-015-0650-8.
280. Kim JS, Shin SY, Kang JH, Yong HS, Na JO, Choi CU, Kim SH, Kim EJ, Rha SW, Park CG, Seo HS, Oh DJ, Hwang C, Kim YH, Lim HE. Infuence of sex on the association between epicardial adipose tissue and left atrial transport function in patients with atrial fbrillation: a multislice computed tomography study. J Am Heart Assoc. 2017;6. pii: e006077. doi: 10.1161/JAHA.117.006077.
281. Kim SA, Kim MN, Shim WJ, Park SM. Epicardial adipose tissue is related to cardiac function in elderly women, but not in men. Nutr Metab Cardiovasc Dis. 2017;27:41-47. doi: 10.1016/j.numecd.2016.11.001.
282. Ahrén B, Månsson S, Gingerich RL, Havel PJ. Regulation of plasma leptin in mice: infuence of age, high-fat diet, and fasting. Am J Physiol. 1997;273(1 Pt 2):R113-R120. doi: 10.1152/ajpregu.1997.273.1.R113.
283. Nakajima H, Terazawa S, Niwano T, Yamamoto Y, Imokawa G. The inhibitory effects of anti-oxidants on ultraviolet-induced up-regulation of the wrinkling-inducing enzyme neutral endopeptidase in human fbroblasts. PLoS One. 2016;11:e0161580. doi: 10.1371/journal.pone.0161580.
284. Nanba K, Vaidya A, Williams GH, Zheng I, Else T, Rainey WE. Age-re-lated autonomous aldosteronism. Circulation. 2017;136:347-355. doi: 10.1161/CIRCULATIONAHA.117.028201.
285. Otsuka H, Yanai M, Kobayashi H, Haketa A, Hara M, Sugama K, Kato K, Soma M. High-molecular-weight adiponectin levels in healthy, community-dwelling, elderly Japanese volunteers: a 5-year prospective observational study [published online ahead of print October 19, 2017]. Aging Clin Exp Res. doi: 10.1007/s40520-017-0840-6.
286. Mulkerrin EC, Brain A, Hampton D, Penney MD, Sykes DA, Williams JD, Coles GA, Woodhouse KW. Reduced renal hemodynamic response to atri-al natriuretic peptide in elderly volunteers. Am J Kidney Dis. 1993;22:538-544.
287. Opie LH, Owen P, du Toit E, Norton GG. Decreased rates of release of atrial natriuretic peptide from isolated hearts from aging hypertensive rats. Am J Hypertens. 1992;5:748-753.
288. Balaskó M, Soós S, Székely M, Pétervári E. Leptin and aging: review and questions with particular emphasis on its role in the central regulation of energy balance. J Chem Neuroanat. 2014;61-62:248-255. doi: 10.1016/j.jchemneu.2014.08.006.
289. Irigoyen MC, Moreira ED, Werner A, Ida F, Pires MD, Cestari IA, Krieger EM. Aging and barorefex control of RSNA and heart rate in rats. Am J Physiol Regul Integr Comp Physiol. 2000;279:R1865-R1871.
290. Iacobellis G, Petramala L, Marinelli C, Calvieri C, Zinnamosca L, Con-cistrè A, Iannucci G, De Toma G, Letizia C. Epicardial fat thickness and primary aldosteronism. Horm Metab Res. 2016;48:238-241. doi: 10.1055/s-0035-1559769.
291. Caprio M, Antelmi A, Chetrite G, Muscat A, Mammi C, Marzolla V, Fabbri A, Zennaro MC, Fève B. Antiadipogenic effects of the mineralocorticoid receptor antagonist drospirenone: potential implications for the treatment of metabolic syndrome. Endocrinology. 2011;152:113-125. doi: 10.1210/en.2010-0674.
292. Wu W, Shi F, Liu D, Ceddia RP, Gaffn R, Wei W, Fang H, Lewandowski ED, Collins S. Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity and insulin resistance. Sci Signal. 2017;10. pii: eaam6870. doi: 10.1126/scisignal.aam6870.
293. Packer M. The alchemist's nightmare: might mesenchymal stem cells that are recruited to repair the injured heart be transformed into fbroblasts rather than cardiomyocytes? Circulation. In Press.
294. Gauss S, Klinghammer L, Steinhoff A, Raaz-Schrauder D, Marwan M, Achenbach S, Garlichs CD. Association of systemic infammation with epi-cardial fat and coronary artery calcifcation. Infamm Res. 2015;64:313-319. doi: 10.1007/s00011-015-0809-x.
295. Wolf G, Ziyadeh FN. Leptin and renal fbrosis. Contrib Nephrol. 2006;151:175-183. doi: 10.1159/000095328.
296. Han DC, Isono M, Chen S, Casaretto A, Hong SW, Wolf G, Ziyadeh FN. Leptin stimulates type I collagen production in db/db mesangial cells: glucose uptake and TGF-beta type II receptor expression. Kidney Int. 2001;59:1315-1323. doi: 10.1046/j.1523-1755.2001.0590041315.x.
297. van Dijk CG, Oosterhuis NR, Xu YJ, Brandt M, Paulus WJ, van Heere-beek L, Duncker DJ, Verhaar MC, Fontoura D, Lourenço A P, Leite-Moreira AF, Falcão-Pires I, Joles JA, Cheng C. Distinct endothelial cell responses in the heart and kidney microvasculature characterize the progression of heart failure with preserved ejection fraction in the obese ZSF1 rat with cardiorenal metabolic syndrome. Circ Heart Fail. 2016;9:e002760. doi 10.1161/CIRCHEARTFAILURE.115.002760
298. Pedone C, Roshanravan B, Scarlata S, Patel KV, Ferrucci L, Incalzi RA Longitudinal association between serum leptin concentration and glo-merular fltration rate in humans. PLoS One. 2015;10:e0117828. doi 10.1371/journal.pone.0117828
299. Stpien M, Stpien A, Wlazeł RN, Paradowski M, Banach M, Rysz M, Rysz J. Obesity indices and adipokines in non-diabetic obese patients with early stages of chronic kidney disease. Med Sci Monit. 2013;19:1063-1072 doi: 10.12659/MSM.889390
300. Petta S, Argano C, Colomba D, Cammà C, Di Marco V, Cabibi D, Tut-tolomondo A, Marchesini G, Pinto A, Licata G, Craxì A. Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: association with the severity of liver disease. J Hepatol 2015;62:928-933. doi: 10 1016/j.jhep.2014.11.030.
301. Cao M, Swigris JJ, Wang X, Cao M, Qiu Y, Huang M, Xiao Y, Cai H Plasma leptin is elevated in acute exacerbation of idiopathic pul-monary fbrosis. Mediators Infamm. 2016;2016:6940480. doi 10.1155/2016/6940480
302. Jain M, Budinger GR, Lo A, Urich D, Rivera SE, Ghosh AK, Gonzalez A, Chiarella SE, Marks K, Donnelly HK, Soberanes S, Varga J, Radigan KA, Chandel NS, Mutlu GM. Leptin promotes fbroproliferative acute respiratory distress syndrome by inhibiting peroxisome proliferator-activated receptor-y. Am J Respir Crit Care Med. 2011;183:1490-1498. doi 10.1164/rccm.201009-1409OC
303. Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CS, Cowie MR, Kjeldsen K, Jankowska EA, Atar D, Butler J, Fiuzat M, Zannad F, Pitt B, O'Connor CM. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol. 2014;64:2281-2293. doi 10.1016/j.jacc.2014.08.036
304. Lana A, Valdés-Bécares A, Buño A, Rodríguez-Artalejo F, Lopez-Garcia E. Serum leptin concentration is associated with incident frailty in older adults. Aging Dis. 2017;8:240-249. doi: 10.14336/AD.2016.0819
305. Song DK, Hong YS, Lee H, Oh JY, Sung YA, Kim Y. Increased epicardial adipose tissue thickness in type 2 diabetes mellitus and obesity. Diabetes Metab J. 2015;39:405-413. doi: 10.4093/dmj.2015.39.5.405
306. Fukuda T, Bouchi R, Terashima M, Sasahara Y, Asakawa M, Takeuchi T, Nakano Y, Murakami M, Minami I, Izumiyama H, Hashimoto K, Yoshimoto T, Ogawa Y. Ipraglifozin reduces epicardial fat accumulation in non-obese type 2 diabetic patients with visceral obesity: a pilot study. Diabetes Ther 2017;8:851-861. doi: 10.1007/s13300-017-0279-y.
307. Suzuki M, Takeda M, Kito A, Fukazawa M, Yata T, Yamamoto M, Nagata T, Fukuzawa T, Yamane M, Honda K, Suzuki Y, Kawabe Y. Tofoglifozin, a sodium/glucose cotransporter 2 inhibitor, attenuates body weight gain and fat accumulation in diabetic and obese animal models. Nutr Diabetes 2014;4:e125. doi: 10.1038/nutd.2014.20
308. Iacobellis G, Mohseni M, Bianco SD, Banga PK. Liraglutide causes large and rapid epicardial fat reduction. Obesity (Silver Spring). 2017;25:311-316. doi: 10.1002/oby.21718
309. Dutour A, Abdesselam I, Ancel P, Kober F, Mrad G, Darmon P, Ronsin O, Pradel V, Lesavre N, Martin JC, Jacquier A, Lefur Y, Bernard M, Gaborit B Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy. Diabetes Obes Metab. 2016;18:882-891. doi: 10.1111/dom.12680
310. Díaz-Rodríguez E, Agra RM, Fernández ÁL, Adrio B, García-Caballero T, González-Juanatey JR, Eiras S. Novel effects of dapaglifozin on epicardial adipose tissue with insulin resistance, high levels of infammatory chemokines production and low differentiation ability. Cardiovasc Res 2018;114:336-346. doi: 10.1093/cvr/cvx186
311. Ye Y, Bajaj M, Yang HC, Perez-Polo JR, Birnbaum Y. SGLT-2 inhibition with dapaglifozin reduces the activation of the Nlrp3/ASC infamma-some and attenuates the development of diabetic cardiomyopathy in mice with type 2 diabetes: further augmentation of the effects with saxa-gliptin, a DPP4 inhibitor. Cardiovasc Drugs Ther. 2017;31:119-132. doi 10.1007/s10557-017-6725-2
312. Pastel E, McCulloch LJ, Ward R, Joshi S, Gooding KM, Shore AC, Kos K. GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction. Clin Sci (Lond). 2017;131:343-353. doi 10.1042/CS20160803
313. Mulvihill EE, Varin EM, Ussher JR, Campbell JE, Bang KW, Abdullah T, Baggio LL, Drucker DJ. Inhibition of dipeptidyl peptidase-4 impairs ventricular function and promotes cardiac fbrosis in high fat-fed diabetic mice. Diabetes. 2016;65:742-754. doi: 10.2337/db15-1224
314. Chu P Y, Zatta A, Kiriazis H, Chin-Dusting J, Du XJ, Marshall T, Kaye DM. CXCR4 antagonism attenuates the cardiorenal consequences of mineralocorticoid excess. Circ Heart Fail. 2011;4:651-658. doi: 10.1161/CIRCHEARTFAILURE.110.960831.
315. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empaglifozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128. doi: 10.1056/NEJMoa1504720.
316. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canaglifozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644-657. doi: 10.1056/NEJMoa1611925.
317. Marso S P, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322. doi: 10.1056/NEJMoa1603827.
318. Altara R, Giordano M, Nordén ES, Cataliotti A, Kurdi M, Bajestani SN, Booz GW. Targeting obesity and diabetes to treat heart failure with preserved ejection fraction. Front Endocrinol (Lausanne). 2017;8:160. doi: 10.3389/fendo.2017.00160.
319. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317-1326. doi: 10.1056/NEJMoa1307684.
320. US Food and Drug Administration. Diabetes medications containing saxa-gliptin and alogliptin: drug safety communication: risk of heart failure. https://www.fda.gov/safety/medwatch/safetyinformation/safetyalerts-forhumanmedicalproducts/ucm494252.htm Accessed April 5, 2016.