Leptin-induced endothelial dysfunction: A target for therapeutic interventions

Current Pharmaceutical Design

Volumn 20, Issue 4, 2014, Pages 603-608

  Payne, Gregory A ^a   Tune, Johnathan D ^b   Knudson, Jarrod D ^c  

^a UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

Author keywords

Cardiovascular disease; Endothelial dysfunction; Endothelium; Leptin; Metabolic syndrome; Perivascular adipose tissue

Indexed keywords

ANGIOTENSIN II; APOLIPOPROTEIN A1; C REACTIVE PROTEIN; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIN 1; GELATINASE A; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; LEPTIN; LEPTIN RECEPTOR; NITRIC OXIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ADIPOSE TISSUE; CARDIOVASCULAR RISK; CELL PROLIFERATION; CORONARY ARTERY BLOOD FLOW; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM; HUMAN; HYPERPLASIA; NEOINTIMA; NONHUMAN; PERIVASCULAR ADIPOSE TISSUE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SMOOTH MUSCLE FIBER; VASCULAR SMOOTH MUSCLE;

ADIPOSE TISSUE; ANIMALS; ATHEROSCLEROSIS; CARDIOVASCULAR AGENTS; DOWN-REGULATION; ENDOTHELIUM, VASCULAR; HUMANS; HYPERPLASIA; LEPTIN; MODELS, CARDIOVASCULAR; MOLECULAR TARGETED THERAPY; SYSTEMIC VASCULITIS; TUNICA INTIMA; UP-REGULATION;

EID: 84894047440     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113199990017     Document Type: Review

References (91)

1. Lembo G, Vecchione C, Fratta L, et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 2000; 49(2): 293-7.
2. Kimura K, Tsuda K, Baba A, et al. Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin. Biochem Biophys Res Commun 2000; 273(2): 745-9.
3. Winters B, Mo Z, Brooks-Asplund E, et al. Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob) mice. J Appl Physiol 2000; 89(6): 2382-90.
4. Nakagawa K, Higashi Y, Sasaki S, et al. Leptin causes vasodilation in humans. Hypertens Res 2002; 25(2): 161-5.
5. Momin AU, Melikian N, Shah AM, et al. Leptin is an endothelialindependent vasodilator in humans with coronary artery disease: Evidence for tissue specificity of leptin resistance. Eur Heart J 2006; 27(19): 2294-9.
6. Hall JE, Jones DW, Kuo JJ, et al. Impact of the obesity epidemic on hypertension and renal disease. Curr Hypertens Rep 2003; 5(5): 386-92.
7. Shirasaka T, Takasaki M, Kannan H. Cardiovascular effects of leptin and orexins. Am J Physiol Regul Integr Comp Physiol 2003; 284(3): R639-51.
8. Matsumura K, Abe I, Tsuchihashi T, et al. Central effects of leptin on cardiovascular and neurohormonal responses in conscious rabbits. Am J Physiol Regul Integr Comp Physiol 2000; 278(5): R1314-20.
9. Fruhbeck G. Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 1999; 48(4): 903-8.
10. Narkiewicz K, Somers VK, Mos L, et al. An independent relationship between plasma leptin and heart rate in untreated patients with essential hypertension. J Hypertens 1999; 17(2): 245-9.
11. Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension 1998; 31(1 Pt 2): 409-14.
12. Dunbar JC, Hu Y, Lu H. Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 1997; 46(12): 2040-3.
13. Haynes WG, Sivitz WI, Morgan DA, et al. Sympathetic and cardiorenal actions of leptin. Hypertension 1997; 30(3 Pt 2): 619-23.
14. Haynes WG, Morgan DA, Walsh SA, et al. Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest 1997; 100(2): 270-8.
15. Beltowski 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(1): 31-40.
16. Pepine CJ. The impact of nitric oxide in cardiovascular medicine: untapped potential utility. Am J Med 2009; 122(5 Suppl): S10-5.
17. Cook S, Hugli O, Egli M, et al. Clustering of cardiovascular risk factors mimicking the human metabolic syndrome X in eNOS null mice. Swiss Med Wkly 2003; 133(25-26): 360-3.
18. Cook S, Vollenweider P, Menard B, et al. Increased eNO and pulmonary iNOS expression in eNOS null mice. Eur Respir J 2003; 21(5): 770-3.
19. Cook S, Scherrer U. Insulin resistance, a new target for nitric oxide-delivery drugs. Fundam Clin Pharmacol 2002; 16(6): 441-53.
20. Duplain H, Burcelin R, Sartori C, et al. Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation 2001; 104(3): 342-5.
21. Piatti P, Di Mario C, Monti LD, et al. Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting. Circulation 2003; 108(17): 2074-81.
22. Vecchione C, Maffei A, Colella S, et al. Leptin effect on endothelial nitric oxide is mediated through Akt-endothelial nitric oxide synthase phosphorylation pathway. Diabetes 2002; 51(1): 168-73.
23. Pardina E, Ferrer R, Baena-Fustegueras JA, et al. The relationships between IGF-1 and CRP, NO, leptin, and adiponectin during weight loss in the morbidly obese. Obes Surg 2010; 20(5): 623-32.
24. Knudson JD, Dincer UD, Zhang C, et al. Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction. Am J Physiol Heart Circ Physiol 2005; 289(1): H48-56.
25. Payne GA, Borbouse L, Kumar S, et al. Epicardial perivascular adipose-derived leptin exacerbates coronary endothelial dysfunction in metabolic syndrome via a protein kinase C-beta pathway. Arterioscler Thromb Vasc Biol 2010; 30(9): 1711-7.
26. Procopio C, Andreozzi F, Laratta E, et al. Leptin-stimulated endothelial nitric-oxide synthase via an adenosine 5'-monophosphate-activated protein kinase/Akt signaling pathway is attenuated by interaction with C-reactive protein. Endocrinology 2009; 150(8): 3584-93.
27. Knudson JD, Dincer UD, Dick GM, et al. Leptin resistance extends to the coronary vasculature in prediabetic dogs and provides a protective adaptation against endothelial dysfunction. Am J Physiol Heart Circ Physiol 2005; 289(3): H1038-46.
28. Biasucci LM, Graziani F, Rizzello V, et al. Paradoxical preservation of vascular function in severe obesity. Am J Med 2010; 123(8): 727-34.
29. Belin de Chantemele EJ, Mintz JD, Rainey WE, et al. Impact of leptin-mediated sympatho-activation on cardiovascular function in obese mice. Hypertension 2011; 58(2): 271-9.
30. Beltowski J, Wojcicka G, Jamroz-Wisniewska A, et al. Resistance to acute NO-mimetic and EDHF-mimetic effects of leptin in the metabolic syndrome. Life Sci 2009; 85(15-16): 557-67.
31. Beltowski J, Wojcicka G, Jamroz-Wisniewska A, et al. Chronic hyperleptinemia induces resistance to acute natriuretic and NOmimetic effects of leptin. Peptides 2010; 31(1): 155-63.
32. Schulze PC, Kratzsch J. Leptin as a new diagnostic tool in chronic heart failure. Clin Chim Acta 2005; 362(1-2): 1-11.
33. Dubey L, Zeng HS, Wang HJ, et al. Potential role of adipocytokine leptin in acute coronary syndrome. Asian Cardiovasc Thorac Ann 2008; 16(2): 124-8.
34. Gruen ML, Hao M, Piston DW, et al. Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis. Am J Physiol Cell Physiol 2007; 293(5): C1481-8.
35. O'Rourke L, Gronning LM, Yeaman SJ, et al. Glucose-dependent regulation of cholesterol ester metabolism in macrophages by insulin and leptin. J Biol Chem 2002; 277(45): 42557-62.
36. Hergenc G, Schulte H, Assmann G, et al. Associations of obesity markers, insulin, and sex hormones with HDL-cholesterol levels in Turkish and German individuals. Atherosclerosis 1999; 145(1): 147-56.
37. Rainwater DL, Comuzzie AG, VandeBerg JL, et al. Serum leptin levels are independently correlated with two measures of HDL. Atherosclerosis 1997; 132(2): 237-43.
38. Shamsuzzaman AS, Winnicki M, Wolk R, et al. Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 2004; 109(18): 2181-5.
39. Kazumi T, Kawaguchi A, Hirano T, et al. C-reactive protein in young, apparently healthy men: associations with serum leptin, QTc interval, and high-density lipoprotein-cholesterol. Metabolism 2003; 52(9): 1113-6.
40. Porreca E, Di Febbo C, Moretta V, et al. Circulating leptin is associated with oxidized LDL in postmenopausal women. Atherosclerosis 2004; 175(1): 139-43.
41. Bouloumie A, Marumo T, Lafontan M, et al. Leptin induces oxidative stress in human endothelial cells. FASEB J 1999; 13(10): 1231-8.
42. De Rosa S, Cirillo P, Pacileo M, et al. Leptin stimulated C-reactive protein production by human coronary artery endothelial cells. J Vasc Res 2009; 46(6): 609-17.
43. Singh P, Hoffmann M, Wolk R, et al. Leptin induces C-reactive protein expression in vascular endothelial cells. Arterioscler Thromb Vasc Biol 2007; 27(9): e302-7.
44. Singh P, Peterson TE, Barber KR, et al. Leptin upregulates the expression of plasminogen activator inhibitor-1 in human vascular endothelial cells. Biochem Biophys Res Commun 2010; 392(1): 47-52.
45. Ren J. Leptin and hyperleptinemia-from friend to foe for cardiovascular function. J Endocrinol 2004; 181(1): 1-10.
46. Karaduman M, Oktenli C, Musabak U, et al. Leptin, soluble interleukin-6 receptor, C-reactive protein and soluble vascular cell adhesion molecule-1 levels in human coronary atherosclerotic plaque. Clin Exp Immunol 2006; 143(3): 452-7.
47. Iribarren C, Husson G, Go AS, et al. Plasma leptin levels and coronary artery calcification in older adults. J Clin Endocrinol Metab 2007; 92(2): 729-32.
48. Schneiderman J, Simon AJ, Schroeter MR, et al. Leptin receptor is elevated in carotid plaques from neurologically symptomatic patients and positively correlated with augmented macrophage density. J Vasc Surg 2008; 48(5): 1146-55.
49. Li L, Mamputu JC, Wiernsperger N, et al. Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin. Diabetes 2005; 54(7): 2227-34.
50. Zeidan A, Purdham DM, Rajapurohitam V, et al. Leptin induces vascular smooth muscle cell hypertrophy through angiotensin IIand endothelin-1-dependent mechanisms and mediates stretchinduced hypertrophy. J Pharmacol Exp Ther 2005; 315(3): 1075-84.
51. Kim JS, Kim IK, Lee SY, et al. Anti-proliferative effect of rosiglitazone on angiotensin II-induced vascular smooth muscle cell proliferation is mediated by the mTOR pathway. Cell Biol Int 2012; 36(3): 305-10.
52. Bienertova-Vasku JA, Hlinomaz O, Vasku A. Are common leptin promoter polymorphisms associated with restenosis after coronary stenting? Heart Vessels 2007; 22(5): 310-5.
53. Shan J, Nguyen TB, Totary-Jain H, et al. Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors. Proc Natl Acad Sci U S A 2008; 105(48): 19006-11.
54. Kim JA, Jang HJ, Martinez-Lemus LA, et al. Activation of mTOR/p70S6 kinase by ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation. Am J Physiol Endocrinol Metab 2012; 302(2): E201-8.
55. Cheng KH, Chu CS, Lee KT, et al. Adipocytokines and proinflammatory mediators from abdominal and epicardial adipose tissue in patients with coronary artery disease. Int J Obes (Lond) 2008; 32(2): 268-74.
56. Mazurek T, Zhang L, Zalewski A, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003; 108(20): 2460-6.
57. Ouwens DM, Sell H, Greulich S, et al. The role of epicardial and perivascular adipose tissue in the pathophysiology of cardiovascular disease. J Cell Mol Med 2010; 14(9): 2223-34.
58. Chatterjee TK, Stoll LL, Denning GM, et al. Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res 2009; 104(4): 541-9.
59. Sacks HS, Fain JN. Human epicardial adipose tissue: a review. Am Heart J 2007; 153(6): 907-17.
60. Payne GA, Kohr MC, Tune JD. Epicardial perivascular adipose tissue as a therapeutic target in obesity-related coronary artery disease. Br J Pharmacol 2012; 165(3): 659-69.
61. Iacobellis G, Gao YJ, Sharma AM. Do cardiac and perivascular adipose tissue play a role in atherosclerosis? Curr Diab Rep 2008; 8(1): 20-4.
62. Greif M, Becker A, von Ziegler F, et al. Pericardial adipose tissue determined by dual source CT is a risk factor for coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2009; 29(5): 781-6.
63. Mahabadi AA, Massaro JM, Rosito GA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J 2009; 30(7): 850-6.
64. Rosito GA, Massaro JM, Hoffmann U, et al. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation 2008; 117(5): 605-13.
65. Ding J, Hsu FC, Harris TB, et al. The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 2009; 90(3): 499-504.
66. Sacks HS, Fain JN, Cheema P, et al. Depot-specific overexpression of proinflammatory, redox, endothelial cell, and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis. Metab Syndr Relat Disord 2011; 9(6): 433-9.
67. Spiroglou SG, Kostopoulos CG, Varakis JN, et al. Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J Atheroscler Thromb 2010; 17(2): 115-30.
68. Gormez S, Demirkan A, Atalar F, et al. Adipose tissue gene expression of adiponectin, tumor necrosis factor-alpha and leptin in metabolic syndrome patients with coronary artery disease. Intern Med 2011; 50(8): 805-10.
69. Shibasaki I, Nishikimi T, Mochizuki Y, et al. Greater expression of inflammatory cytokines, adrenomedullin, and natriuretic peptide receptor-C in epicardial adipose tissue in coronary artery disease. Regul Pept 2010; 165(2-3): 210-7.
70. Langheim S, Dreas L, Veschini L, et al. Increased expression and secretion of resistin in epicardial adipose tissue of patients with acute coronary syndrome. Am J Physiol Heart Circ Physiol 2010; 298(3): H746-53.
71. Jaffer I, Riederer M, Shah P, et al. Expression of fat mobilizing genes in human epicardial adipose tissue. Atherosclerosis 2012; 220(1): 122-7.
72. Eringa EC, Bakker W, van Hinsbergh VW. Paracrine regulation of vascular tone, inflammation and insulin sensitivity by perivascular adipose tissue. Vascul Pharmacol 2012.
73. Houben AJ, Eringa EC, Jonk AM, et al. Perivascular Fat and the Microcirculation: Relevance to Insulin Resistance, Diabetes, and Cardiovascular Disease. Curr Cardiovasc Risk Rep 2012; 6(1): 80-90.
74. Aghamohammadzadeh R, Withers S, Lynch F, et al. Perivascular adipose tissue from human systemic and coronary vessels: the emergence of a new pharmacotherapeutic target. Br J Pharmacol 2012; 165(3): 670-82.
75. Huang F, Lezama MA, Ontiveros JA, et al. Effect of losartan on vascular function in fructose-fed rats: the role of perivascular adipose tissue. Clin Exp Hypertens 2010; 32(2): 98-104.
76. Gao YJ, Takemori K, Su LY, et al. Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion. Cardiovasc Res 2006; 71(2): 363-73.
77. Knudson JD, Dincer UD, Bratz IN, et al. Mechanisms of coronary dysfunction in obesity and insulin resistance. Microcirculation 2007; 14(4-5): 317-38.
78. Bunker AK, Laughlin MH. Influence of exercise and perivascular adipose tissue on coronary artery vasomotor function in a familial hypercholesterolemic porcine atherosclerosis model. J Appl Physiol 2010; 108(3): 490-7.
79. Reifenberger MS, Turk JR, Newcomer SC, et al. Perivascular fat alters reactivity of coronary artery: effects of diet and exercise. Med Sci Sports Exerc 2007; 39(12): 2125-34.
80. Barandier C, Montani JP, Yang Z. Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity. Am J Physiol Heart Circ Physiol 2005; 289(5): H1807-13.
81. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med 1999; 340(2): 115-26.
82. Beltowski J, Wojcicka G, Marciniak A, et al. Oxidative stress, nitric oxide production, and renal sodium handling in leptininduced hypertension. Life Sci 2004; 74(24): 2987-3000.
83. Payne GA, Borbouse L, Bratz IN, et al. Endogenous adiposederived factors diminish coronary endothelial function via inhibition of nitric oxide synthase. Microcirculation 2008; 15(5): 417-26.
84. Payne GA, Bohlen HG, Dincer UD, et al. Periadventitial adipose tissue impairs coronary endothelial function via PKC-betadependent phosphorylation of nitric oxide synthase. Am J Physiol Heart Circ Physiol 2009; 297(1): H460-5.
85. Ma L, Ma S, He H, et al. Perivascular fat-mediated vascular dysfunction and remodeling through the AMPK/mTOR pathway in high-fat diet-induced obese rats. Hypertens Res 2010; 33(5): 446-53.
86. Ketonen J, Shi J, Martonen E, et al. Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in dietinduced obese C57Bl/6 mice. Circ J 2010; 74(7): 1479-87.
87. Marchesi C, Ebrahimian T, Angulo O, et al. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome. Hypertension 2009; 54(6): 1384-92.
88. Venugopal SK, Devaraj S, Jialal I. Effect of C-reactive protein on vascular cells: evidence for a proinflammatory, proatherogenic role. Curr Opin Nephrol Hypertens 2005; 14(1): 33-7.
89. Sierra-Johnson J, Romero-Corral A, Lopez-Jimenez F, et al. Relation of increased leptin concentrations to history of myocardial infarction and stroke in the United States population. Am J Cardiol 2007; 100(2): 234-9.
90. Sun YM, Li J, Luan Y, et al. Effect of statin therapy on leptin levels in patients with coronary heart disease. Peptides 2010; 31(6): 1205-7.
91. Chen Y, Ohmori K, Mizukawa M, et al. Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes. Circ J 2007; 71(1): 144-52.