Local Application of Leptin Antagonist Attenuates Angiotensin II-Induced Ascending Aortic Aneurysm and Cardiac Remodeling

Journal of the American Heart Association

Volumn 5, Issue 5, 2016, Pages

  Ben Zvi, Danny ^a   Savion, Naphtali ^b   Kolodgie, Frank ^c   Simon, Amos ^b   Fisch, Sudeshna ^d   Schäfer, Katrin ^e   Bachner Hinenzon, Noa ^f   Cao, Xin ^d   Gertler, Arieh ^g   Solomon, Gili ^g   Kachel, Erez ^b   Raanani, Ehud ^b   Lavee, Jacob ^b   Kotev Emeth, Shlomo ^b   Virmani, Renu ^c   Schoen, Frederick J ^h   Schneiderman, Jacob ^b,d  

^a Harvard University   (United States)

^b TEL AVIV UNIVERSITY   (Israel)

^c CVPATH INSTITUTE   (United States)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

^e JOHANNES GUTENBERG UNIVERSITY   (Germany)

^f Analyze IT Research Institute   (Israel)

^g HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^h HARVARD MIT DIVISION OF HEALTH SCIENCES AND TECHNOLOGY   (United States)

Author keywords

Angiotensin II; Aortic aneurysm; Aortic valve stenosis; Left ventricular hypertrophy; Leptin; Leptin antagonist; Vascular remodeling

Indexed keywords

ANGIOTENSIN II; APOLIPOPROTEIN E; HORMONE ANTAGONIST; LEPTIN; LEPTIN ANTAGONIST; MESSENGER RNA; UNCLASSIFIED DRUG; VASOCONSTRICTOR AGENT;

ADULT; AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTIC ANEURYSM; ARTICLE; ASCENDING AORTIC ANEURYSM; CELL PROLIFERATION; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; GENE EXPRESSION; HEART DILATATION; HEART PROTECTION; HEART VENTRICLE REMODELING; HORMONE SYNTHESIS; HUMAN; HUMAN CELL; HUMAN TISSUE; LOW DRUG DOSE; MALE; MIDDLE AGED; MITRAL VALVE; MOUSE; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; THORACIC AORTA ANEURYSM; VERY ELDERLY; YOUNG ADULT; ANIMAL; ANTAGONISTS AND INHIBITORS; AORTIC VALVE; AORTIC VALVE STENOSIS; APOLIPOPROTEIN E KNOCKOUT MOUSE; ARTERIAL STIFFNESS; CELL CULTURE; CHEMICALLY INDUCED; CYTOLOGY; DRUG EFFECTS; HEART LEFT VENTRICLE HYPERTROPHY; METABOLISM;

ADULT; AGED; AGED, 80 AND OVER; ANGIOTENSIN II; ANIMALS; AORTIC ANEURYSM, THORACIC; AORTIC VALVE; AORTIC VALVE STENOSIS; CELL PROLIFERATION; CELLS, CULTURED; FEMALE; HUMANS; HYPERTROPHY, LEFT VENTRICULAR; LEPTIN; MALE; MICE; MICE, KNOCKOUT, APOE; MIDDLE AGED; VASCULAR STIFFNESS; VASOCONSTRICTOR AGENTS; VENTRICULAR REMODELING; YOUNG ADULT;

EID: 84991339470     PISSN: None     EISSN: 20479980     Source Type: Journal    
DOI: 10.1161/JAHA.116.003474     Document Type: Article

References (54)

1. Davies RR, Goldstein LJ, Coady MA, Tittle SL, Rizzo JA, Kopf GS, Elefteriades JA. Yearly rupture or dissection rates for thoracic aortic aneurysms: simple prediction based on size. Ann Thorac Surg. 2002;73:17-27; discussion 27-8.
2. Danyi P, Elefteriades JA, Jovin IS. Medical therapy of thoracic aortic aneurysms: are we there yet? Circulation. 2011;124:1469-1476.
3. Isselbacher EM. Thoracic and abdominal aortic aneurysms. Circulation. 2005;111:816-828.
4. Lindsay ME, Dietz HC. Lessons on the pathogenesis of aneurysm from heritable conditions. Nature. 2011;473:308-316.
5. Tadros TM, Klein MD, Shapira OM. Ascending aortic dilatation associated with bicuspid aortic valve: pathophysiology, molecular biology, and clinical implications. Circulation. 2009;119:880-890.
6. Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC III. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med. 2008;358:2787-2795.
7. Gallo EM, Loch DC, Habashi JP, Calderon JF, Chen Y, Bedja D, van Erp C, Gerber EE, Parker SJ, Sauls K, Judge DP, Cooke SK, Lindsay ME, Rouf R, Myers L, ap Rhys CM, Kent KC, Norris RA, Huso DL, Dietz HC. Angiotensin II-dependent TGF-beta signaling contributes to Loeys-Dietz syndrome vascular pathogenesis. J Clin Invest. 2014;124:448-460.
8. Silverberg D, Younis A, Savion N, Harari G, Yakubovitch D, Sheick Yousif B, Halak M, Grossman E, Schneiderman J. Long-term renin-angiotensin blocking therapy in hypertensive patients with normal aorta may attenuate the formation of abdominal aortic aneurysms. J Am Soc Hypertens. 2014;8:571-577.
9. Daugherty A, Manning MW, Cassis LA. Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest. 2000;105:1605-1612.
10. -/- mice. Clin Sci. 2010;118:681-689.
11. Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312:117-121.
12. Favreau JT, Nguyen BT, Gao I, Yu P, Tao M, Schneiderman J, Gaudette GR, Ozaki CK. Murine ultrasound imaging for circumferential strain analyses in the angiotensin II abdominal aortic aneurysm model. J Vasc Surg. 2012;56:462-469.
13. Raaz U, Zollner AM, Schellinger IN, Toh R, Nakagami F, Brandt M, Emrich FC, Kayama Y, Eken S, Adam M, Maegdefessel L, Hertel T, Deng A, Jagger A, Buerke M, Dalman RL, Spin JM, Kuhl E, Tsao PS. Segmental aortic stiffening contributes to experimental abdominal aortic aneurysm development. Circulation. 2015;131:1783-1795.
14. Tao M, Yu P, Nguyen BT, Mizrahi B, Savion N, Kolodgie FD, Virmani R, Hao S, Ozaki CK, Schneiderman J. Locally applied leptin induces regional aortic wall degeneration preceding aneurysm formation in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2013;33:311-320.
15. Wang Y, Ait-Oufella H, Herbin O, Bonnin P, Ramkhelawon B, Taleb S, Huang J, Offenstadt G, Combadiere C, Renia L, Johnson JL, Tharaux PL, Tedgui A, Mallat Z. TGF-beta activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice. J Clin Invest. 2010;120:422-432.
16. Martinez-Martinez E, Miana M, Jurado-Lopez R, Bartolome MV, Souza Neto FV, Salaices M, Lopez-Andres N, Cachofeiro V. The potential role of leptin in the vascular remodeling associated with obesity. Int J Obes (Lond). 2014;38:1565-1572.
17. Rosenbaum M, Nicolson M, Hirsch J, Heymsfield SB, Gallagher D, Chu F, Leibel RL. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab. 1996;81:3424-3427.
18. Schneiderman J, Schaefer K, Kolodgie FD, Savion N, Kotev-Emeth S, Dardik R, Simon AJ, Halak M, Pariente C, Engelberg I, Konstantinides S, Virmani R. Leptin locally synthesized in carotid atherosclerotic plaques could be associated with lesion instability and cerebral emboli. J Am Heart Assoc. 2012;1:e001727 doi: 10.1161/JAHA.112.001727.
19. Cecelja M, Chowienczyk P. Role of arterial stiffness in cardiovascular disease. JRSM Cardiovasc Dis. 2012;1:1-10.
20. Ejiri J, Inoue N, Tsukube T, Munezane T, Hino Y, Kobayashi S, Hirata K, Kawashima S, Imajoh-Ohmi S, Hayashi Y, Yokozaki H, Okita Y, Yokoyama M. Oxidative stress in the pathogenesis of thoracic aortic aneurysm: protective role of statin and angiotensin II type 1 receptor blocker. Cardiovasc Res. 2003;59:988-996.
21. Parhami F, Tintut Y, Ballard A, Fogelman AM, Demer LL. Leptin enhances the calcification of vascular cells: artery wall as a target of leptin. Circ Res. 2001;88:954-960.
22. Simonds SE, Pryor JT, Ravussin E, Greenway FL, Dileone R, Allen AM, Bassi J, Elmquist JK, Keogh JM, Henning E, Myers MG Jr, Licinio J, Brown RD, Enriori PJ, O'Rahilly S, Sternson SM, Grove KL, Spanswick DC, Farooqi IS, Cowley MA. Leptin mediates the increase in blood pressure associated with obesity. Cell. 2014;159:1404-1416.
23. Soderberg S, Ahren B, Jansson JH, Johnson O, Hallmans G, Asplund K, Olsson T. Leptin is associated with increased risk of myocardial infarction. J Intern Med. 1999;246:409-418.
24. Sun Z. Aging, arterial stiffness, and hypertension. Hypertension. 2015;65:252-256.
25. Boonyasirinant T, Rajiah P, Setser RM, Lieber ML, Lever HM, Desai MY, Flamm SD. Aortic stiffness is increased in hypertrophic cardiomyopathy with myocardial fibrosis: novel insights in vascular function from magnetic resonance imaging. J Am Coll Cardiol. 2009;54:255-262.
26. Eren M, Gorgulu S, Uslu N, Celik S, Dagdeviren B, Tezel T. Relation between aortic stiffness and left ventricular diastolic function in patients with hypertension, diabetes, or both. Heart. 2004;90:37-43.
27. Redheuil A, Yu WC, Mousseaux E, Harouni AA, Kachenoura N, Wu CO, Bluemke D, Lima JA. Age-related changes in aortic arch geometry: relationship with proximal aortic function and left ventricular mass and remodeling. J Am Coll Cardiol. 2011;58:1262-1270.
28. Mottram PM, Haluska BA, Leano R, Carlier S, Case C, Marwick TH. Relation of arterial stiffness to diastolic dysfunction in hypertensive heart disease. Heart. 2005;91:1551-1556.
29. Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002;106:2085-2090.
30. Huggins CE, Domenighetti AA, Pedrazzini T, Pepe S, Delbridge LM. Elevated intracardiac angiotensin II leads to cardiac hypertrophy and mechanical dysfunction in normotensive mice. J Renin Angiotensin Aldosterone Syst. 2003;4:186-190.
31. Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. J Clin Invest. 1990;86:1913-1920.
32. Zablocki D, Sadoshima J. Solving the cardiac hypertrophy riddle: the angiotensin II-mechanical stress connection. Circ Res. 2013;113:1192-1195.
33. 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.
34. Glader CA, Birgander LS, Soderberg S, Ildgruben HP, Saikku P, Waldenstrom A, Dahlen GH. Lipoprotein(a), Chlamydia pneumoniae, leptin and tissue plasminogen activator as risk markers for valvular aortic stenosis. Eur Heart J. 2003;24:198-208.
35. Helske S, Lindstedt KA, Laine M, Mayranpaa M, Werkkala K, Lommi J, Turto H, Kupari M, Kovanen PT. Induction of local angiotensin II-producing systems in stenotic aortic valves. J Am Coll Cardiol. 2004;44:1859-1866.
36. Fujisaka T, Hoshiga M, Hotchi J, Takeda Y, Jin D, Takai S, Hanafusa T, Ishizaka N. Angiotensin II promotes aortic valve thickening independent of elevated blood pressure in apolipoprotein-E deficient mice. Atherosclerosis. 2013;226:82-87.
37. Le Quang K, Bouchareb R, Lachance D, Laplante MA, El Husseini D, Boulanger MC, Fournier D, Fang XP, Avramoglu RK, Pibarot P, Deshaies Y, Sweeney G, Mathieu P, Marette A. Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014;34:2283-2291.
38. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008;88:389-419.
39. Shpilman M, Niv-Spector L, Katz M, Varol C, Solomon G, Ayalon-Soffer M, Boder E, Halpern Z, Elinav E, Gertler A. Development and characterization of high affinity leptins and leptin antagonists. J Biol Chem. 2011;286:4429-4442.
40. Daugherty A, Rateri DL, Lu H, Inagami T, Cassis LA. Hypercholesterolemia stimulates angiotensin peptide synthesis and contributes to atherosclerosis through the AT1A receptor. Circulation. 2004;110:3849-3857.
41. Leung JC, Chan LY, Tang SC, Chu KM, Lai KN. Leptin induces TGF-beta synthesis through functional leptin receptor expressed by human peritoneal mesothelial cell. Kidney Int. 2006;69:2078-2086.
42. Aikawa E, Nahrendorf M, Sosnovik D, Lok VM, Jaffer FA, Aikawa M, Weissleder R. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation. 2007;115:377-386.
43. Grotenhuis HB, Ottenkamp J, Westenberg JJM, Bax JJ, Kroft LJM, de Roos A. Reduced aortic elasticity and dilation are associated with aortic regurgitation and left ventricular hypertrophy in nonstenotic bicuspid aortic valve patients. J Am Coll Cardiol. 2007;49:1660-1665.
44. Liu AC, Joag VR, Gotlieb AI. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am J Pathol. 2007;171:1407-1418.
45. Aikawa E, Whittaker P, Farber M, Mendelson K, Padera RF, Aikawa M, Schoen FJ. Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering. Circulation. 2006;113:1344-1352.
46. Schoen FJ. Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation. 2008;118:1864-1880.
47. Jian B, Narula N, Li QY, Mohler ER III, Levy RJ. Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg. 2003;75:457-465; discussion 465-6.
48. Merryman WD, Lukoff HD, Long RA, Engelmayr GC Jr, Hopkins RA, Sacks MS. Synergistic effects of cyclic tension and transforming growth factor-beta1 on the aortic valve myofibroblast. Cardiovasc Pathol. 2007;16:268-276.
49. Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999;341:142-147.
50. Drazner MH. The progression of hypertensive heart disease. Circulation. 2011;123:327-334.
51. Police SB, Thatcher SE, Charnigo R, Daugherty A, Cassis LA. Obesity promotes inflammation in periaortic adipose tissue and angiotensin II-induced abdominal aortic aneurysm formation. Arterioscler Thromb Vasc Biol. 2009;29:1458-1464.
52. Bisping E, Wakula P, Poteser M, Heinzel FR. Targeting cardiac hypertrophy: toward a causal heart failure therapy. J Cardiovasc Pharmacol. 2014;64:293-305.
53. Lacro RV, Dietz HC, Sleeper LA, Yetman AT, Bradley TJ, Colan SD, Pearson GD, Selamet Tierney ES, Levine JC, Atz AM, Benson DW, Braverman AC, Chen S, De Backer J, Gelb BD, Grossfeld PD, Klein GL, Lai WW, Liou A, Loeys BL, Markham LW, Olson AK, Paridon SM, Pemberton VL, Pierpont ME, Pyeritz RE, Radojewski E, Roman MJ, Sharkey AM, Stylianou MP, Wechsler SB, Young LT, Mahony L; Pediatric Heart Network I. Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med. 2014;371:2061-2071.
54. Nadir MA, Wei L, Elder DH, Libianto R, Lim TK, Pauriah M, Pringle SD, Doney AD, Choy AM, Struthers AD, Lang CC. Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis. J Am Coll Cardiol. 2011;58:570-576.