Leptin and vascular smooth muscle cells

Current Pharmaceutical Design

Volumn 20, Issue 4, 2014, Pages 625-634

  Trovati, Mariella ^a   Doronzo, Gabriella ^a   Barale, Cristina ^a   Vaccheris, Claudia ^a   Russo, Isabella ^a   Cavalot, Franco ^a  

^a UNIVERSITY OF TURIN   (Italy)

Author keywords

Atherosclerosis; Insulin resistance; Leptin; Leptin resistance; Nitric oxide; Obesity; Restenosis; Vascular calcification; Vascular smooth muscle cells

Indexed keywords

ANGIOTENSIN; ANGIOTENSIN II; ENDOTHELIN; ENDOTHELIN 1; INDUCIBLE NITRIC OXIDE SYNTHASE; INSULIN; JANUS KINASE; LEPTIN; LEPTIN RECEPTOR; MAMMALIAN TARGET OF RAPAMYCIN; METALLOPROTEINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE P38; NITRIC OXIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; STAT PROTEIN;

ARTERY CALCIFICATION; ATHEROGENESIS; ATHEROSCLEROSIS; CELL DIFFERENTIATION; CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; ENDOTHELIUM CELL; HUMAN; HYPERLEPTINEMIA; IN VITRO STUDY; INSULIN RESISTANCE; INTRACELLULAR SIGNALING; NONHUMAN; OBESITY; OSTEOBLAST; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS; REVIEW; SMOOTH MUSCLE FIBER; UPREGULATION; VASCULAR SMOOTH MUSCLE; VASCULAR SMOOTH MUSCLE CELL;

ANIMALS; ATHEROSCLEROSIS; CELL MOVEMENT; CELL PROLIFERATION; HUMANS; HYPERTROPHY; LEPTIN; MODELS, CARDIOVASCULAR; MUSCLE, SMOOTH, VASCULAR; PROTEIN ISOFORMS; RECEPTORS, LEPTIN; SIGNAL TRANSDUCTION; UP-REGULATION;

EID: 84894073331     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113199990022     Document Type: Review

References (134)

1. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-32.
2. Ahima RS. Central actions of adipocyte hormones. Trends Endocrinol Metab 2005; 16: 307-13.
3. Ahima RS, Osei SY. Leptin signalling. Physiol Behav 2004; 81: 223-41.
4. Gorska E, Popko K, Stelmaszczyk-Emmel A, et al. Leptin receptors. Eur J Med Res 2010; 15, Suppl.2: 50-4.
5. Wauman J, Tavernier J. Leptin receptor signalling: pathways to leptin resistance. Front Biosci 2011; 17:2771-93.
6. Tartaglia LA. The leptin receptor. J Biol Chem 1997; 272: 6093-6.
7. Frühbeck G. Intracellular signalling pathways activated by leptin. Biochem J 2006; 393: 7-20.
8. Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903-8.
9. Tups A. Physiological models of leptin resistance. J Neuroendocrinol 2009; 21: 961-971.
10. Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab 2009; 297: E1247-59.
11. Myers MG Jr, Leibel RL, Seeley RJ, et al. Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab 2010; 21: 643-51.
12. Munzberg H. Leptin-signaling pathways and leptin resistance. Forum Nutr 2010; 63: 123-132.
13. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292-5.
14. Enriori PJ, Evans AE, Sinnayah P, Cowley MA. Leptin resistance and obesity. Obesity (Silver Spring) 2006; 14 Suppl 5: 254S-258S.
15. Schroeter MR, Schneiderman J, Schumann B, et al. Expression of the leptin receptor in different types of vascular lesions. Histochem Cell Biol 2007; 128: 323-33.
16. Rahmouni K and Haynes W. Leptin and the cardiovascular system. J Endocrinology 2004; 225-44.
17. Ren LJ. Leptin and hyperleptinemia-from friend to foe for cardiovascular function. J Endocrinol 2004; 181: 1-10.
18. Beltowski J. Leptin and atherosclerosis. Atherosclerosis 2006; 189: 47-60.
19. Beltowski J. Role of leptin in blood pressure regulation and arterial hypertension. J Hypertens 2006; 24: 789-801.
20. Dubey L and Hesong Z. Role of leptin in atherogenesis. Exp Clin Cardiol. 2006; 11: 269-75.
21. Anfossi G, Russo I, Doronzo G, et al. Adipokines in atherothrombosis: focus on platelets and vascular smooth muscle cells. Mediators Inflamm 2010; 2010: 1-26.
22. Maenhaut N, Van de Voorde J. Regulation of vascular tone by adipocytes. BMC Med 2011; 9: 1-12.
23. Beltowski J. Leptin and the regulation of endothelial function in physiological and pathological conditions. Clin Exp Pharmacol Physiol 2012; 39: 168-78.
24. Söderberg S, Ahrén B, Jansson JH, et al. Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999; 246: 409-18.
25. Thogersen AM, Soderberg S, Jansson JH, et al. Interactions between fibrinolysis, lipoproteins and leptin related to a first myocardial infarction. Eur J Cardiovasc Prev Rehabil 2004; 11: 33-40.
26. Wallerstedt SM, Eriksson AL, Niklason A, et al. Serum leptin and myocardial infarction in hypertension. Blood Press 2004; 13: 243-6.
27. Wallace AM, McMahon AC, Packard CJ, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation 2001; 104: 3052-6.
28. Singhal A, Farooqi IS, Cole TJ, et al. Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation 2002; 106: 1919-24.
29. Sundell J, Huupponen R, Raitakari OT, et al. High serum leptin is associated with attenuated coronary vasoreactivity. Obes Res 2003; 11: 776-82.
30. Ciccone M, Vettor R, Pannacciulli N, et al. Plasma leptin is independently associated with the intima-media thickness of the common carotid artery. Int J Obes Relat Metab Disord 2001; 25: 805-10.
31. Wolk R, Berger P, Lennon RJ, et al. Plasma leptin and prognosis in patients with established coronary atherosclerosis. J Am Coll Cardiol 2004; 44: 1819-24.
32. Reilly MP, Iqbal N, Schutta M, et al. Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 3872-78.
33. Qasim A, Metha NN, Tadesse MG, et al. Adipokines, insulin resistance and coronary artery calcification. J Am Coll Cardiol 2008; 52: 231-36.
34. Piatti P, Di Mario C, Monti LC, et al. Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with instent restenosis in patients undergoing coronary stenting. Circulation 2003; 108: 2074-81.
35. Stephenson K, Tunstead J, Tsai A, et al. Neointimal formation after endovascular arterial injury is markedly attenuated in db/db mice. Arterioscler Thromb Vasc Biol 2003; 23: 2027-33.
36. Schäfer K, Halle M, Goeschen C, et al. Leptin promotes vascular remodeling and neointimal growth in mice. Arterioscler Thromb Vasc Biol 2004; 24: 112-17.
37. Stamler JS, Dzau VJ, Loscalzo J. The vascular smooth muscle cell. In: Loscalzo J, Creager MA and Dzau J, Editors. Vascular medicine: A textbook of vascular biology and diseases. 2nd edn Boston/ New York/Toronto/London: Little Brown and Company Editions 1996; pp. 69-116.
38. Berk BC. Vascular smooth muscle growth: autocrine growth mechanisms. Physiol Rev 2001; 81: 999-1030.
39. Rivard A, Andres V. Vascular smooth muscle cell proliferation in the pathogenesis of atherosclerotic cardiovascular diseases. Histol Histopathol 2000; 15: 557-71.
40. Willis AI, Pierre-Paul D, Sumpio BE, et al. Vascular smooth muscle cell migration: current research and clinical implications. Vasc Endovasc Surg 2004; 38: 11-23.
41. House SJ, Potier M, Bisaillon J, et al. The non-excitable smooth muscle: calcium signaling and phenotypic switching during vascular disease. Plugers Arch 2008; 465: 769-85.
42. Cecchettini A, Rocchiccioli S, Boccardi C, et al. Vascular smoothmuscle cell activation: proteomics point of view. Int Rev Cell Mol Biol 2011; 288: 43-99.
43. Shanahan CM, Weissberg PL. Smooth muscle heterogeneity: patterns of gene expression in vascular smooth muscle cells in vitro and in vivo. Arterioscler Thromb Vasc Biol 1998; 18: 333-8.
44. Rzucidlo EM, Martin KA, Powell RJ. Regulation of vascular smooth muscle cell differentiation. J Vasc Surg 2007; 45: A25-32.
45. Clarke M, Bennett M. The emerging role of vascular smooth muscle cell apoptosis in atherosclerosis and plaque stability. Am J Nephrol 2006; 26: 531-35.
46. Oda A, Taniguchi T, Yokoyama M. Leptin stimulates rat aortic smooth muscle cell proliferation and migration. Kobe J Med Sci 2001; 47: 141-50.
47. Bodary PF, Shen Y, Ohman M, et al. Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance. Arterioscler Thromb Vasc Biol 2007; 27: 70-76.
48. Juan CC, Chuang TY, Lien CC, et al. Leptin increases endothelin type A receptor levels in vascular smooth muscle cells. Am J Physiol Endocrinol Metab 2008; 294: E481-87.
49. Sweeney G. Leptin signaling. Cell Signal 2002; 14: 655-63.
50. Zeidan A, Paylor B, Steinhoff KJ, et al. Actin cytoskeleton dynamics promotes leptin-induced vascular smooth muscle hypertrophy via RhoA/ROCK-and phosphatidylinositol 3-kinase/protein kinase B-dependent pathways. J Pharmacol Exp Ther 2007; 322: 1110-6.
51. Shimokawa H, Takeshita A. Rho-Kinase Is an Important Therapeutic Target in Cardiovascular Medicine. Arterioscler Thromb and Vasc Biol 2005; 25: 1767-75.
52. Shan J, Nguyen TB, Totary-Jain H, et al. Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors. Proc Natl Acad Sci USA 2008; 105: 19006-11.
53. Zargham R. Preventing restenosis after angioplasty: a multistage approach. Clin Sci (Lond) 2008; 114: 257-64.
54. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003; 349: 1315-23.
55. Higaki M and Shimokado K. Phosphatidylinositol 3-kinase is required for growth factor-induced amino acid uptake by vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1999; 19: 2127-32.
56. Brazil DP, Park J, Hemmings BA. PKB binding proteins. Getting in on the Akt. Cell 2002; 111: 293-303.
57. Liu Y, Shanahan CM. Signalling pathways and vascular calcification. Front Biosci 2011; 16: 1302-14.
58. Takahashi E, Berk BC. MAP kinases and vascular smooth muscle function. Acta Physiol Scand 1998; 164: 611-21.
59. Shin HJ, Oh J, Kang SM, et al. Leptin induces hypertrophy via p38 mitogen-activated protein kinase in rat vascular smooth muscle cells. Biochem Biophys Res Commun 2005; 329: 18-24.
60. 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: 2227-34.
61. Newby AC, Southgate KM, Davies M. Extracellular matrix degrading metalloproteinases in the pathogenesis of arteriosclerosis. Basic Res Cardiol 1994; 89: 59-70.
62. Newby AC. Matrix metalloproteinases regulate migration, proliferation and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates. Cardiovasc Res 2006; 69: 614-24.
63. Paravicini TM, Touyz RM. Redox signalling in hypertension. Cardiovasc Res 2006; 71: 247-58.
64. Satoh K, Nigro P, Berk BC. Oxidative stress and vascular smooth muscle cell growth: a mechanistic linkage by cyclophilin A. Antioxid Redox Signal 2010; 12: 675-82.
65. Schroeter MR, Stein S, Heida NM, et al. Leptin promotes the mobilization of vascular progenitor cells and neovascularization by NOX2-mediated activation of MMP9. Cardiovasc Res. 2012; 93: 170-80.
66. UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-65.
67. Ajchenbaum F, Ando K, DeCaprio JA, et al. Independent regulation of human D-type cyclin gene expression during G1 phase in primary human T lymphocytes. J Biol Chem 1993; 268: 4113-19.
68. Huang F, Xiong X, Wang H, et al. Leptin-induced vascular smooth muscle cell proliferation via regulating cell cycle, activating ERK1/2 and NF-kappaB. Acta Biochim Biophys Sin (Shanghai) 2010; 42: 325-31.
69. Bohlen F, Kratzsch J, Mueller M, et al. Leptin inhibits cell growth of human vascular smooth muscle cells. Vascul Pharmacol. 2007; 46: 67-71.
70. Rodríguez A, Gómez-Ambrosi J, Catalán V, et al. Leptin inhibits the proliferation of vascular smooth muscle cells induced by angiotensin II through nitric oxide-dependent mechanisms. Mediators Inflamm 2010; 2010: 105489.
71. Parhami F, Tintut Y, Ballard A, et al. Leptin enhances the calcification of vascular cells: artery wall as a target of leptin. Circ Res 2001; 88: 954-60.
72. Zeadin M, Butcher M, Werstuck G, et al. Effect of leptin on vascular calcification in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2009; 29: 2069-75.
73. Zeadin MG, Butcher MK, Shaughnessy SG, Werstuck GH. Leptin promotes osteoblast differentiation and mineralization of primary cultures of vascular smooth muscle cells by inhibiting glycogen synthase kinase (GSK)-3β. Biochem Biophys Res Commun 2012; 425: 924-30.
74. Shroff RC, Shanahan CM. The vascular biology of calcification. Semin Dial 2007; 20: 103-9.
75. Iribarren C, Sidney S, Sternfeld B, et al. Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. JAMA 2000; 283: 2810-2815.
76. Arad Y, Spadaro LA, Goodman K, Newstein D, et al. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol 2000; 36: 1253-60.
77. Vliegenthart R, Oudkerk M, Song B, et al. Coronary calcification detected by electron-beam computed tomography and myocardial infarction. The Rotterdam Coronary Calcification Study. Eur Heart J 2002; 23: 1596-1603.
78. Haude M, Erbel R, Straub U. Results of intracoronary stents for management of coronary dissection after balloon angioplasty. Am J Cardiol 1991; 67: 691-96.
79. Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection after angioplasty: an observational study using intravascular ultrasound. Circulation 1992; 86: 64-70.
80. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331: 496-501.
81. Virmani R, Farb A, Burke AP. Coronary angioplasty from the perspective of atherosclerotic plaque: morphological predictors of immediate success and restenosis. Am Heart J 1994; 127: 163-79.
82. Hahn AW, Resink TJ, Kern F, et al. Peptide vasoconstrictors, vessel structure, and vascular smooth-muscle proliferation. J Cardiovasc Pharmacol 1993; 22 (Suppl.5) S37-43.
83. Touyz RM, Tabet F, Schiffrin EL. Redox-dependent signalling by angiotensin II and vascular remodelling in hypertension. Clin Exp Pharmacol Physiol 2003; 30: 860-6.
84. Touyz RM. Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension: role of angiotensin II. Exp Physiol 2005; 90: 449-55.
85. Little P, Ivey ME, Osman N. Endothelin-1 actions on vascular smooth muscle cell functions as a target for the prevention of atherosclerosis. Curr Vasc Pharmacol 2008; 6: 195-203.
86. 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: 1075-84.
87. Shaw A, Xu Q. Biomechanical stress-induced signalling in smooth muscle cells: an update. Curr Vasc Pharmacol 2003; 1: 41-58.
88. Haga JH, Li YS, Chien S. Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells. J Biomech 2007; 40: 947-60.
89. Halka At, Turner NJ, Carter A, et al. The effects of stretch on vascular smooth muscle cell phenotype in vitro. Cardiovasc Pathol 2008; 17: 98-102.
90. Chao H-H, Hong H-J, Liu J-C, et al. Leptin stimulates endothelin-1 expression via extracellular signal-regulated kinase by epidermal growth factor receptor transactivation in rat aortic smooth muscle cells. Eur J Pharmacol 2007; 573: 49-54.
91. Ferri C, Bellini C, Desideri G, et al. Plasma endothelin-1 levels in obese hypertensive and normotensive men. Diabetes 1995; 44: 431-36.
92. Eguchi S, Frank GD, Mifune M, et al. Metalloprotease-dependent ErbB ligand shedding in mediating EGFR transactivation and vascular remodelling. Biochem Soc Trans 2003; 31: 1198-1202.
93. Jamroz-Wisniewska A, Wojcicka G, Lowicka E, et al. Transactivation of epidermal growth factor receptor in vascular and renal systems in rats with experimental hyperleptinemia: role in leptininduced hypertension. Biochem Pharmacol 2008; 75: 1623-38.
94. Fortuño A, Rodríguez A, Gómez-Ambrosi J, et al. Leptin inhibits angiotensin II-induced intracellular calcium increase and vasoconstriction in the rat aorta. Endocrinology 2002; 143: 3555-60.
95. Rodríguez A, Frühbeck G, Gómez-Ambrosi J, et al. The inhibitory effect of leptin on angiotensin II-induced vasoconstriction is blunted in spontaneously hypertensive rats. J Hypertens. 2006; 24: 1589-97.
96. Rodríguez A, Fortuño A, Gómez-Ambrosi J, et al. The inhibitory effect of leptin on angiotensin II-induced vasoconstriction in vascular smooth muscle cells is mediated via a nitric oxide-dependent mechanism. Endocrinology 2007; 148: 324-31.
97. Afroze T, Husain M. Cell cycle dependent regulation of intracellular calcium concentration in vascular smooth muscle cells: a potential target for drug therapy. Curr Drug Target Cardiovasc Haematol Disord 2001; 1: 23-40.
98. Trovati M, Massucco P, Mattiello L, et al. Insulin increases cyclic nucleotide content in human vascular smooth muscle cells: a mechanism potentially involved in insulin-induced modulation of vascular tone. Diabetologia 1995; 38:936-41.
99. Trovati M, Massucco P, Mattiello L, et al. Human vascular smooth muscle cells express a constitutive nitric oxide synthase that insulin rapidly activates, thus increasing guanosine 3':5'-cyclic monophosphate and adenosine 3':5'-cyclic monophosphate concentrations. Diabetologia 1999; 42: 831-9.
100. Lincoln TM, Wu X, Sellak H, et al. Regulation of vascular smooth muscle cell phenotype by cyclic GMP and cyclic GMP-dependent protein kinase. Front Biosci 2006; 11: 356-67.
101. Kibbe M, Billiar T, Tzeng E. Inducible nitric oxide synthase and vascular injury. Cardiovasc Res 1999; 43: 650-7.
102. Hecker M, Cattaruzza M, Wagner AH. Regulation of inducible nitric oxide synthase gene expression in vascular smooth muscle cells. Gen Pharmacol 1999; 32: 9-16.
103. Correia ML, Haynes WG. Leptin, obesity and cardiovascular disease. Curr Opin Nephrol Hypertens 2004; 13: 215-23.
104. Sharma V, McNeill JH. The emerging roles of leptin and ghrelin in cardiovascular physiology and pathophysiology. Curr Vasc Pharmacol 2005; 3: 169-80.
105. Frühbeck G. Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 1999; 48: 903-8.
106. Lembo G, Vecchione C, Fratta L, et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes. 2000; 49(2):293-7.
107. 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: 168-73.
108. Procopio C, Andreozzi F, Laratta E, et al. Leptin-stimulated endothelial nitric-oxide synthase via an adenosine 5'-monophosphateactivated protein kinase/Akt signaling pathway is attenuated by interaction with C-reactive protein. Endocrinology. 2009; 150: 3584-93.
109. Vecchione C, Aretini A, Maffei A, et al. Cooperation between insulin and leptin in the modulation of vascular tone. Hypertension 2003; 42: 166-70.
110. Benkhoff S, Loot AE, Pierson I, et al. Leptin potentiates endothelium-dependent relaxation by inducing endothelial expression of neuronal NO synthase. Arterioscler Thromb Vasc Biol 2012; 32: 1605-12.
111. Wójcicka G, Jamroz-Wiśniewska A, Widomska S, Ksiazek M, Bełtowski J. Role of extracellular signal-regulated kinases (ERK) in leptin-induced hypertension. Life Sci 2008; 82: 402-12.
112. Beltowski J, Wójcicka G, Marciniak A, Jamroz A. Oxidative stress, nitric oxide production, and renal sodium handling in leptininduced hypertension. Life Sci 2004; 74: 2987-3000.
113. Beltowski J. Effect of hyperleptinemia on endothelial nitric oxide production. Atherosclerosis 2005; 178: 403-4.
114. 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.
115. Bełtowski J, Wójcicka G, Jamroz-Wiśniewska A, Marciniak A. Resistance to acute NO-mimetic and EDHF-mimetic effects of leptin in the metabolic syndrome. Life Sci 2009; 85: 557-67.
116. Korda M, Kubant R, Patton S, Malinski T. Leptin-induced endothelial dysfunction in obesity. Am J Physiol Heart Circ Physiol 2008; 295: H1514-21.
117. Schinzari F, Tesauro M, Rovella V, et al. Leptin stimulates both endothelin-1 and nitric oxide activity in lean subjects but not in patients with obesity-related metabolic syndrome. J Clin Endocrinol Metab 2013; 98: 1235-41.
118. Miao CY, Li ZY. The role of perivascular adipose tissue in vascular smooth muscle cell growth. Br J Pharmacol 2012; 165: 643-58.
119. Gálvez-Prieto B, Somoza B, Gil-Ortega M, et al. Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension. Front Pharmacol 2012; 3: 103.
120. Ahanchi SS, Tsihlis ND, Kibbe MR. The role of nitric oxide in the pathophysiology of intimal hyperplasia. J Vasc Surg 2007; 45: A64-73.
121. Chatterjee A, Black SM, Catravas JD. Endothelial nitric oxide (NO) and its pathophysiologic regulation. Vascul Pharmacol 2008; 49: 134-40.
122. Joffin N, Niang F, Forest C, Jaubert AM. Is there NO help for leptin? Biochimie 2012; 94: 2104-10.
123. Ignarro LJ, Lippton H, Edwards JC, et al. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther 1981; 218: 739-49.
124. Arnold WP, Mittal CK, Katsuki S, Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci U S A 1977; 74: 3203-7.
125. Yu Q, Gao F, Ma XL. Insulin says NO to cardiovascular disease. Cardiovasc Res 2011; 89: 516-24.
126. Muniyappa R, Sowers JR. Role of insulin resistance in endothelial dysfunction. Rev Endocr Metab Disord 2013; 14: 5-12.
127. Doronzo G, Russo I, Mattiello L, et al. Insulin activates vascular endothelial growth factor in vascular smooth muscle cells: influence of nitric oxide and of insulin resistance. Eur J Clin Invest 2004; 34: 664-673.
128. Doronzo G, Russo I, Mattiello L, et al. Insulin activates hypoxiainducible factor 1alpha in human rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling. Diabetologia 2006; 49: 1049-63
129. Russo I, Del Mese P, Doronzo G, et al. Resistance to the nitric oxide/cyclic guanosine 5'-monophosphate/protein kinase G pathway in vascular smooth muscle cells fro the obse Zucker rat, a classical animal model of insulin resistance: role of oxidative stress. Endocrinology 2008; 149: 1480-9
130. Doronzo G, Viretto M, Russo I, et al. Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: influence of insulin resistance and oxidative stress. Atherosclerosis 2011; 216: 44-53.
131. Anfossi G, Russo I, Doronzo G, et al. Relevance of the vascular effects of insulin in the rationale of its therapeutical use. Cardiovasc Hematol Disord Drug Targets 2007: 7: 228-49.
132. Anfossi G, Russo I, Doronzo G, et al. Contribution of insulin resistance to vascular dysfunction. Arch Physiol Biochem 2009; 115: 199-217.
133. Anfossi G, Cavalot F, Massucco P, et al. Insulin influences immunoreactive endothelin release by human vascular smooth muscle cells. Metabolism 1993; 42: 1081-3.
134. Cavalot F, Russo I, Mattiello L, et al. Influence of protamine on adhesion, chemotaxis and proliferation of human vascular smooth muscle cells. Diabetologia 1997; 40: 67-75.