Adipokines, vascular wall, and cardiovascular disease: A focused overview of the role of adipokines in the pathophysiology of cardiovascular disease

Angiology

Volumn 66, Issue 1, 2015, Pages 8-24

  Maresca, Fabio ^a   Di Palma, Vito ^a   Bevilacqua, Michele ^a   Uccello, Giuseppe ^a   Taglialatela, Vittorio ^a   Giaquinto, Alessandro ^a   Esposito, Giovanni ^a   Trimarco, Bruno ^a   Cirillo, Plinio ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Acute coronary syndrome; Adipokines; Atherosclerosis; Cardiovascular disease; Inflammation; Obesity; Vascular wall

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; APELIN; LEPTIN; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; OMENTIN; RESISTIN; RETINOL BINDING PROTEIN 4; UNCLASSIFIED DRUG; VASPIN; AUTACOID; BIOLOGICAL MARKER;

ADIPOSE TISSUE; BLOOD VESSEL WALL; CARDIOVASCULAR DISEASE; HUMAN; MOLECULAR PATHOLOGY; NONALCOHOLIC FATTY LIVER; PROTEIN FUNCTION; REVIEW; ADIPOCYTE; ANIMAL; BLOOD; BLOOD VESSEL; CARDIOVASCULAR DISEASES; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; PATHOPHYSIOLOGY; RISK FACTOR; SIGNAL TRANSDUCTION;

ADIPOCYTES; ADIPOKINES; ANIMALS; BIOLOGICAL MARKERS; BLOOD VESSELS; CARDIOVASCULAR DISEASES; HUMANS; INFLAMMATION MEDIATORS; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; RISK FACTORS; SIGNAL TRANSDUCTION;

EID: 84927172678     PISSN: 00033197     EISSN: 19401574     Source Type: Journal    
DOI: 10.1177/0003319713520463     Document Type: Review

References (295)

1. World Health Organization. World Health Statistics 2012. Geneva: World Health Organization; 2012.
2. World Health Organization. Global Health Risks: Mortality and Burden of Disease Attributable to Selected Major Risks. Geneva: World Health Organization; 2009.
3. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083-1096.
4. Phillips SD, Roberts WC. Comparison of body mass index among patients with versus without angiographic coronary artery disease. Am J Cardiol. 2007;100(1):18-22.
5. Buettner HJ, Mueller C, Gick M, et al. The impact of obesity on mortality in UA/non-ST-segment elevation myocardial infarction. Eur Heart J. 2007;28(14):1694-1701.
6. Faber DR, de Groot PG, Visseren FL. Role of adipose tissue in haemostasis, coagulation and fibrinolysis. Obes Rev. 2009; 10(5):554-563.
7. Sowers J.R. Obesity as a cardiovascular risk factor. Am J Med. 2003;115 suppl 8A:37S-41S.
8. Attie AD, Scherer PE. Adipocyte metabolism and obesity. J Lipid Res. 2009;50 suppl:S395-S399.
9. Deng Y, Scherer PE. Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci. 2010;1212: E1-E19.
10. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. Characteristics other than the diagnostic criteria associated with metabolic syndrome: an overview. Curr Vasc Pharmacol. 2014; 12(4):627-641.
11. Soumaya K. Molecular mechanisms of insulin resistance in diabetes. Adv Exp Med Biol. 2012;771:240-251.
12. Kadoglou NP, Iliadis F, Angelopoulou N, et al. The antiinflammatory effects of exercise training in patients with type 2 diabetes mellitus. Eur J Cardiovasc Prev Rehabil. 2007;14(6): 837-843.
13. Athyros VG, Tziomalos K, Karagiannis A, Anagnostis P, Mikhailidis DP. Should adipokines be considered in the choice of the treatment of obesity-related health problems? Curr Drug Targets. 2010;11(1):122-135.
14. Katsiki N, Mikhailidis DP, Gotzamani-Psarrakou A, Yovos JG, Karamitsos D. Effect of various treatments on leptin, adiponectin, ghrelin and neuropeptide Y in patients with type 2 diabetes mellitus. Expert Opin Ther Targets. 2011;15(4):401-420.
15. Katsiki N, Nikolic D, Montalto G, Banach M, Mikhailidis DP, Rizzo M. The role of fibrate treatment in dyslipidemia: an overview. Curr Pharm Des. 2013;19(17):3124-3131.
16. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316(2):129-139.
17. Trujillo ME, Scherer PE. Adipose tissue-derived factors: impact on health and disease. Endocr Rev. 2006;27(7):762-778.
18. Avram AS, Avram MM, James WD. Subcutaneous fat in normal and diseased states: 2. Anatomy and physiology of white and brown adipose tissue. J Am Acad Dermatol. 2005;53(4):671-683.
19. Ailhaud G. Adipose tissue as a secretory organ: from adipogenesis to the metabolic syndrome. C R Biol. 2006;329(8):570-577.
20. Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114(12):1752-1761.
21. Hosogai N, Fukuhara A, Oshima K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes. 2007;56(4):901-911.
22. Pachler C, Ikeoka D, Plank J, et al. Subcutaneous adipose tissue exerts proinflammatory cytokines after minimal trauma in humans. Am J Physiol Endocrinol Metab. 2007;293(3):E690-E696.
23. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796-1808.
24. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85-97.
25. Katsiki N, Mikhailidis DP, Wierzbicki AS. Epicardial fat and vascular risk: a narrative review. Curr Opin Cardiol. 2013;28(4): 458-463.
26. de Feyter PJ. Epicardial adipose tissue: an emerging role for the development of coronary atherosclerosis. Clin Cardiol. 2011; 34(3):143-144.
27. van der Giessen AG, Gijsen FJ, Wentzel JJ, et al. Small coronary calcifications are not detectable by 64-slice contrast enhanced computed tomography. Int J Cardiovasc Imaging. 2011;27(1): 143-152.
28. de Vos AM, Prokop M, Roos CJ, et al. Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women. Eur Heart J. 2008;29(6):777-783.
29. Gorter PM, van Lindert AS, de Vos AM, et al. Quantification of epicardial and peri-coronary fat using cardiac computed tomography; reproducibility and relation with obesity and metabolic syndrome in patients suspected of coronary artery disease. Atherosclerosis. 2008;197(2):896-903.
30. 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):781-786.
31. 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):850-856.
32. Ueno K, Anzai T, Jinzaki M, et al. Increased epicardial fat volume quantified by 64-multidetector computed tomography is associated with coronary atherosclerosis and totally occlusive lesions. Circ J. 2009;73(10):1927-1933.
33. Yong HS, Kim EJ, Seo HS, et al. Pericardial fat is more abundant in patients with coronary atherosclerosis and even in the non-obese patients: evaluation with cardiac ct angiography. Int J Cardiovasc Imaging. 2010;26 suppl:153-162.
34. Konishi M, Sugiyama S, Sugamura K, et al. Association of pericardial fat accumulation rather than abdominal obesity with coronary atherosclerotic plaque formation in patients with suspected coronary artery disease. Atherosclerosis. 2010;209(2):573-578.
35. Henrichot E, Juge Aubry CE, Pernin A, et al. Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis? Arterioscler Thromb Vasc Biol. 2005;25(12): 2594-2259.
36. 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):210-217.
37. Baker AR, Silva NF, Quinn DW, et al. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc Diabetol. 2006;5:1.
38. 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):268-274.
39. 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):805-810.
40. Iacobellis G, Pistilli D, Gucciardo M, et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29(6):251-255.
41. Mazurek T, Zhang L, Zalewski A, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003; 108(20):2460-2466.
42. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to c1q, produced exclusively in adipocytes. J Biol Chem. 1995;270(45):26746-26749.
43. Takahashi M, Arita Y, Yamagata K, et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord. 2000;24(7):861-868.
44. Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79-83.
45. Hasan-Ali H, Abd El-Mottaleb NA, Hamed HB, Abd-Elsayed A. Serum adiponectin and leptin as predictors of the presence and degree of coronary atherosclerosis. Coron Artery Dis. 2011; 22(4):264-269.
46. Liang KW, Sheu WH, Lee WL, et al. Decreased circulating protective adiponectin level is associated with angiographic coronary disease progression in patients with angina pectoris. Int J Cardiol. 2008;129(1):76-80.
47. Eroglu S, Sade LE, Bozbas H, et al. Association of serumadiponectin levels and coronary flowreserve in women with normal coronary angiography. Eur J Cardiovasc Prev Rehabil. 2009;16(3):290-296.
48. Kojima S, Funahashi T, Sakamoto T, et al. The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction. Heart. 2003;89(6):667.
49. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004;291(14):1730-1737.
50. Schulze MB, Shai I, Rimm EB, Li T, Rifai N, Hu FB. Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes. 2005;54(2):534-539.
51. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2004; 24(1):29-33.
52. Bobbert T, Rochlitz H, Wegewitz U, et al. Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes. 2005;54(9):2712-2719.
53. Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipocyte-secreted hormone acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. J Biol Chem. 2003; 278(11):9073-9085.
54. Ebinuma H, Miyazaki O, Yago H, Hara K, Yamauchi T, Kadowaki T. A novel ELISA system for selective measurement of human adiponectin multimers by using proteases. Clin Chim Acta. 2006;372(1-2):47-53.
55. Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT. Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes. 2006;55(1):249-259.
56. Murdolo G, Nowotny B, Celi F, et al. Inflammatory adipokines, high molecular weight adiponectin, and insulin resistance: a population-based survey in prepubertal schoolchildren. PLoS One. 2011;6(2):e17264.
57. Stofkova A. Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity. Endocr Regul. 2009;43(4):157-168.
58. Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem. 2003;278(4):2461-2468.
59. Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF. T-cadherin is a receptor for hexameric and high-molecularweight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA. 2004;101(28):10308-10313.
60. Doyle DD, Goings GE, Upshaw-Earley J, Page E, Ranscht B, Palfrey HC. T-cadherin is a major glycophosphoinositolanchored protein associated with noncaveolar detergentinsoluble domains of the cardiac sarcolemma. J Biol Chem. 1998;273(12):6937-6943.
61. Fujioka D, Kawabata K, Saito Y, et al. Role of adiponectin receptors in endothelin-induced cellular hypertrophy in cultured cardiomyocytes and their expression in infarcted heart. Am J Physiol Heart Circ Physiol. 2006;290(6):H2409-H24016.
62. Yamauchi T, Nio Y, Maki T, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007;13(3):332-339.
63. Tan KC, Xu A, Chow WS, et al. Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab. 2004;89(2):765-769.
64. Fesus G, Dubrovska G, Gorzelniak K, et al. Adiponectin is a novel humoral vasodilator. Cardiovasc Res. 2007;75(4):719-727.
65. Xi W, Satoh H, Kase H, Suzuki K, Hattori Y. Stimulated HSP90 binding to eNOS and activation of the PI3-Akt pathway contribute to globular adiponectin-induced no production: vasorelaxation in response to globular adiponectin. Biochem Biophys Res Commun. 2005;332(1):200-205.
66. Greenstein AS, Khavandi K, Withers SB, et al. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009;119(12): 1661-1670.
67. Chen X, Zhang H, McAfee S, Zhang C. The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice. Am J Physiol Heart Circ Physiol. 2010;299(3):H605-H612.
68. Ouedraogo R, Gong Y, Berzins B, et al. Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Invest. 2007;117(6):1718-1726.
69. Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999;100(25):2473-2476.
70. Arita Y, Kihara S, Ouchi N, et al. Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BBbinding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation. 2002;105(24):2893-2898.
71. Cai XJ, Chen L, Li L, et al. Adiponectin inhibits lipopolysaccharide- induced adventitial fibroblastmigration and transition to myofibroblasts via AdipoR1-AMPK-iNOS pathway. Mol Endocrinol. 2010;24(1):218-228.
72. Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class a scavenger receptor expression in human monocyte-derived macrophages. Circulation. 2001;103(8):1057-1063.
73. Tian L, Luo N, Klein RL, Chung BH, Garvey WT, Fu Y. Adiponectin reduces lipid accumulation in macrophage foam cells. Atherosclerosis. 2009;202(1):152-161.
74. Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002; 106(22):2767-2770.
75. Okamoto Y, Folco EJ, Minami M, et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res. 2008;102(2):218-225.
76. Kato H, Kashiwagi H, Shiraga M, et al. Adiponectin acts as an endogenous antithrombotic factor. Arterioscler Thromb Vasc Biol. 2006;26(1):224-230.
77. Hall JE. The kidney, hypertension, and obesity. Hypertension. 2003;41(3 pt 2):625-633.
78. Kim DH, Kim C, Ding EL, Townsend MK, Lipsitz LA. Adiponectin levels and the risk of hypertension: a systematic review and meta-analysis. Hypertension. 2013;62(1):27-32.
79. Shibata R, Ouchi N, Ito M, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004;10(12): 1384-1389.
80. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26(3):439-451.
81. Karmazyn M, Purdham DM, Rajapurohitam V, Zeidan A. Signalling mechanisms underlying the metabolic and other effects of adipokines on the heart. Cardiovasc Res. 2008;79(2): 279-286.
82. Ouchi N, Shibata R, Walsh K. Cardioprotection by adiponectin. Trends Cardiovasc Med. 2006;16(5):141-146.
83. Shibata R, Sato K, Pimentel DR, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPKand COX-2-dependent mechanisms. Nat Med. 2005;11(10): 1096-1103.
84. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425-432.
85. Auwerx J, Staels B. Leptin. Lancet. 1998;351(9104):737-742.
86. Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995;269(5223):540-543.
87. Dieguez C, Vazquez MJ, Romero A, Lopez M, Nogueiras R. Hypothalamic control of lipid metabolism: focus on leptin, ghrelin and melanocortins. Neuroendocrinology. 2011;94(1):1-11.
88. Buettner C, Muse ED, Cheng A, et al. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med. 2008;14(6):667-675.
89. Mantzoros CS, Magkos F, Brinkoetter M, et al. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab. 2011;301(4):E567-E584.
90. Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV. Leptin: the tale of an obesity gene. Diabetes. 1996;45(11): 1455-1462.
91. Zabeau L, Lavens D, Peelman F, Eyckerman S, Vandekerckhove J, Tavernier J. The ins and outs of leptin receptor activation. FEBS Lett. 2003;546(1):45-50.
92. Minokoshi Y, Kim YB, Peroni OD, et al. Leptin stimulates fattyacid oxidation by activating AMP-activated protein kinase. Nature. 2002;415(6869):339-343.
93. Ren J. Leptin and hyperleptinemia-from friend to foe for cardiovascular function. J Endocrinol. 2004;181(1):1-10.
94. Sahu A. Minireview: a hypothalamic role in energy balance with special emphasis on leptin. Endocrinology. 2004;145(6): 2613-2620.
95. Fruhbeck G. Intracellular signalling pathways activated by leptin. Biochem J. 2006;393(pt 1):7-20.
96. Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord. 2002;26(11):1407-1433.
97. Gnacinska M, Malgorzewicz S, Stojek M, Lysiak-Szydlowska W, Sworczak K. Role of adipokines in complications related to obesity: a review. Adv Med Sci. 2009;54(2):150-157.
98. ConsidineRV, SinhaMK,HeimanML, et al. Serumimmunoreactiveleptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334(5):292-295.
99. Enriori PJ, Evans AE, Sinnayah P, Cowley M.A. Leptin resistance and obesity. Obesity (Silver Spring). 2006;14 suppl 5:254S-258S.
100. Wauman J, Tavernier J. Leptin receptor signaling: pathways to leptin resistance. Front Biosci (Landmark Ed). 2011;16: 2771-2793.
101. Soderberg S, Ahren B, Jansson JH, et al. Leptin is associated with increased risk of myocardial infarction. J Intern Med. 1999;246(4):409-418.
102. Soderberg S, Ahren B, Stegmayr B, et al. Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke. 1999;30(2):328-337.
103. Taneli F, Yegane S, Ulman C, et al. Increased serum leptin concentrations in patients with chronic stable angina pectoris and ST-elevated myocardial infarction. Angiology. 2006;57(3): 267-272.
104. Wallace AM, McMahon AD, Packard CJ, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001; 104(25):3052-3056.
105. Wolk R, Berger P, Lennon RJ, Brilakis ES, Johnson BD, Somers VK. Plasma leptin and prognosis in patients with established coronary atherosclerosis. J Am Coll Cardiol. 2004;44(9): 1819-1824.
106. 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):2074-2081.
107. Norata GD, Raselli S, Grigore L, et al. Leptin:adiponectin ratio is an independent predictor of intima media thickness of the common carotid artery. Stroke. 2007;38(10):2844-2846.
108. Beltowski J. Leptin and atherosclerosis. Atherosclerosis. 2006; 189(1):47-60.
109. Lembo G, Vecchione C, Fratta L, et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes. 2000;49(2):293-297.
110. 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):168-173.
111. Beltowski J. Leptin and the regulation of endothelial function in physiological and pathological conditions. Clin Exp Pharmacol Physiol. 2012;39(2):168-178.
112. Trovati M, Doronzo G, Barale C, Vaccheris C, Russo I, Cavalot F. Leptin and vascular smooth muscle cells. Curr Pharm Des. 2014;20(4):625-634.
113. Konstantinides S, Schafer K, Koschnick S, Loskutoff DJ. Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J Clin Invest. 2001;108(10):1533-1540.
114. Bodary PF, Westrick RJ, Wickenheiser KJ, Shen Y, Eitzman DT. Effect of leptin on arterial thrombosis following vascular injury in mice. JAMA. 2002;287(13):1706-1709.
115. Bodary PF, Gu S, Shen Y, Hasty AH, Buckler JM, Eitzman DT. Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005;25(8):e119-e122.
116. Cirillo P, Angri V, De Rosa S, et al. Pro-atherothrombotic effects of leptin in human coronary endothelial cells. Thromb Haemost. 2010;103(5):1065-1075.
117. Napoleone E, DIS A, Amore C, et al. Leptin induces tissue factor expression in human peripheral blood mononuclear cells: a possible link between obesity and cardiovascular risk? J Thromb Haemost. 2007;5(7):1462-1468.
118. Bouloumie A, Marumo T, Lafontan M, Busse R. Leptin induces oxidative stress in human endothelial cells. FASEB J. 1999; 13(10):1231-1238.
119. Schafer K, Konstantinides S. Mechanisms linking leptin to arterial and venous thrombosis: potential pharmacological targets. Curr Pharm Des. 2014;20(4):635-640.
120. De Rosa S, Cirillo P, Pacileo M, Di Palma V, Paglia A, Chiariello M. Leptin stimulated C-reactive protein production by human coronary artery endothelial cells. J Vasc Res. 2009; 46(6):609-617.
121. Cirillo P, Golino P, Calabro P, et al. C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation. Cardiovasc Res. 2005;68(1): 47-55.
122. Zeadin M, Butcher M, Werstuck G, Khan M, Yee CK, Shaughnessy SG. Effect of leptin on vascular calcification in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2009;29(12):2069-2075.
123. Chiba T, Shinozaki S, Nakazawa T, et al. Leptin deficiency suppresses progression of atherosclerosis in apoE-deficient mice. Atherosclerosis. 2008;196(1):68-75.
124. Nickola MW, Wold LE, Colligan PB, Wang GJ, Samson WK, Ren J. Leptin attenuates cardiac contraction in rat ventricular myocytes. Role of no. Hypertension. 2000;36(4):501-505.
125. Dong F, Zhang X, Ren J. Leptin regulates cardiomyocyte contractile function through endothelin-1 receptor-NADPH oxidase pathway. Hypertension. 2006;47(2):222-229.
126. Madani S, De Girolamo S, Munoz DM, Li RK, Sweeney G. Direct effects of leptin on size and extracellular matrix components of human pediatric ventricular myocytes. Cardiovasc Res. 2006;69(3):716-725.
127. Rajapurohitam V, Gan XT, Kirshenbaum LA, Karmazyn M. The obesity-associated peptide leptin induces hypertrophy in neonatal rat ventricular myocytes. Circ Res. 2003;93(4):277-279.
128. Tajmir P, Ceddia RB, Li RK, Coe IR, Sweeney G. Leptin increases cardiomyocyte hyperplasia via extracellular signalregulated kinase- and phosphatidylinositol 3-kinase-dependent signaling pathways. Endocrinology. 2004;145(4):1550-1555.
129. Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection. Cardiovasc Res. 2004;61(3): 372-385.
130. Erkasap N, Ikizler M, Shneyvays V, et al. Leptin protects the cardiac myocyte cultures from hypoxic damage. Life Sci. 2006;78(10):1098-1102.
131. Smith CC, Mocanu MM, Davidson SM, Wynne AM, Simpkin JC, Yellon DM. Leptin, the obesity-associated hormone, exhibits direct cardioprotective effects. Br J Pharmacol. 2006;149(1): 5-13.
132. Smith CC, Dixon RA, Wynne AM, et al. Leptin-induced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore. Am J Physiol Heart Circ Physiol. 2010;299(4):H1265-H1270.
133. 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(6):H2877-H2884.
134. Steppan CM, Brown EJ, Wright CM, et al. A family of tissuespecific resistin-like molecules. Proc Natl Acad Sci USA. 2001;98(2):502-506.
135. Adeghate E. An update on the biology and physiology of resistin. Cell Mol Life Sci. 2004;61(19-20):2485-2496.
136. Filkova M, Haluzik M, Gay S, Senolt L. The role of resistin as a regulator of inflammation: implications for various human pathologies. Clin Immunol. 2009;133(2):157-170.
137. Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307-312.
138. Yaturu S, Daberry RP, Rains J, Jain S. Resistin and adiponectin levels in subjects with coronary artery disease and type 2 diabetes. Cytokine. 2006;34(3-4):219-223.
139. Burnett MS, Lee CW, Kinnaird TD, et al. The potential role of resistin in atherogenesis. Atherosclerosis. 2005;182(2):241-248.
140. Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation. 2005;111(7):932-939.
141. Rajala MW, Qi Y, Patel HR, et al. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes. 2004;53(7):1671-1679.
142. Qi Y, Nie Z, Lee YS, et al. Loss of resistin improves glucose homeostasis in leptin deficiency. Diabetes. 2006;55(11): 3083-3090.
143. Kunnari A, Ukkola O, Paivansalo M, Kesaniemi YA. High plasma resistin level is associated with enhanced highly sensitive c-reactive protein and leukocytes. J Clin Endocrinol Metab. 2006;91(7):2755-2760.
144. Lubos E, Messow CM, Schnabel R, et al. Resistin, acute coronary syndrome and prognosis results from the atherogene study. Atherosclerosis. 2007;193(1):121-128.
145. Norata GD, Ongari M, Garlaschelli K, Raselli S, Grigore L, Catapano AL. Plasma resistin levels correlate with determinants of the metabolic syndrome. Eur J Endocrinol. 2007; 156(2):279-284.
146. Wang H, Chen DY, Cao J, He ZY, Zhu BP, Long M. High serum resistin level may be an indicator of the severity of coronary disease in acute coronary syndrome. Chin Med Sci J. 2009;24(3): 161-166.
147. Pischon T, Bamberger CM, Kratzsch J, et al. Association of plasma resistin levels with coronary heart disease in women. Obes Res. 2005;13(10):1764-1771.
148. Chu S, Ding W, Li K, Pang Y, Tang C. Plasma resistin associated with myocardium injury in patients with acute coronary syndrome. Circ J. 2008;72(8):1249-1253.
149. 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-H753.
150. Efstathiou SP, Tsiakou AG, Tsioulos DI, et al. Prognostic significance of plasma resistin levels in patients with atherothrombotic ischemic stroke. Clin Chim Acta. 2007;378(1-2):78-85.
151. Verma S, Li SH, Wang CH, et al. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation. 2003;108(6):736-740.
152. Li Y, Wang Y, Li Q, et al. Effect of resistin on vascular endothelium secretion dysfunction in rats. Endothelium. 2007;14(4-5): 207-214.
153. Calabro P, Samudio I, Willerson JT, Yeh ET. Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3- kinase pathways. Circulation. 2004;110(21):3335-3340.
154. Jung HS, Park KH, Cho YM, et al. Resistin is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovasc Res. 2006;69(1):76-85.
155. Calabro P, Cirillo P, Limongelli G, et al. Tissue factor is induced by resistin in human coronary artery endothelial cells by the NF-kB-dependent pathway. J Vasc Res. 2011;48(1):59-66.
156. Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 2005;307(5708):426-430.
157. Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre- B-cell colony-enhancing factor. Mol Cell Biol. 1994;14(2): 1431-1437.
158. Rongvaux A, Shea RJ, Mulks MH, et al. Pre-B-cell colonyenhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyl transferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol. 2002;32(11):3225-3234.
159. Tan BK, Chen J, Digby JE, Keay SD, Kennedy CR, Randeva HS. Increased visfatin messenger ribonucleic acid and protein levels in adipose tissue and adipocytes in women with polycystic ovary syndrome: parallel increase in plasma visfatin. J Clin Endocrinol Metab. 2006;91(12):5022-5028.
160. Berndt J, Kloting N, Kralisch S, et al. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes. 2005;54(10):2911-2916.
161. Wang P, Xu TY, Guan YF, Su DF, Fan GR, Miao CY. Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide. Cardiovasc Res. 2009;81(2):370-380.
162. Saddi-Rosa P, Oliveira CS, Giuffrida FM, Reis AF. Visfatin, glucose metabolism and vascular disease: a review of evidence. Diabetol Metab Syndr. 2010;2:21.
163. Wang Z, Nakayama T. Inflammation, a link between obesity and cardiovascular disease. Mediators Inflamm. 2010;2010:535918.
164. Kadoglou NP, Sailer N, Moumtzouoglou A, et al. Visfatin (NAMPT) and ghrelin as novel markers of carotid atherosclerosis in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2010;118(2):75-80.
165. Zhong M, Tan HW, Gong HP, Wang SF, Zhang Y, Zhang W. Increased serum visfatin in patients with metabolic syndrome and carotid atherosclerosis. Clin Endocrinol (Oxf). 2008;69(6): 878-884.
166. Liu SW, Qiao SB, Yuan JS, Liu DQ. Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans. Clin Endocrinol (Oxf). 2009; 71(2):202-207.
167. Dahl TB, Yndestad A, Skjelland M, et al. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. Circulation. 2007;115(8):972-980.
168. Spiroglou SG, Kostopoulos CG, Varakis JN, Papadaki HH. Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis. J Atheroscler Thromb. 2010;17(2):115-130.
169. Lu L-F, Wang C-P, Yu T-H, et al. Interpretation of elevated plasma visfatin concentrations in patients with ST-elevation myocardial infarction. Cytokine. 2012;57(1):74-80.
170. Adya R, Tan BK, Punn A, Chen J, Randeva HS. Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatininduced angiogenesis. Cardiovasc Res. 2008;78(2):356-365.
171. Yamawaki H, Hara N, Okada M, Hara Y. Visfatin causes endothelium-dependent relaxation in isolated blood vessels. Biochem Biophys Res Commun. 2009;383(4):503-508.
172. Takebayashi K, Suetsugu M, Wakabayashi S, Aso Y, Inukai T. Association between plasma visfatin and vascular endothelial function in patients with type 2 diabetes mellitus. Metabolism. 2007;56(4):451-458.
173. Kim SR, Bae YH, Bae SK, et al. Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells. Biochim Biophys Acta. 2008; 1783(5):886-895.
174. Cirillo P, Di Palma V, Maresca F, et al. The adipokine visfatin induces tissue factor expression in human coronary artery endothelial cells: another piece in the adipokines puzzle. Thromb Res. 2012;130(3):403-408.
175. Moschen AR, Kaser A, Enrich B, et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol. 2007;178(3):1748-1758.
176. Lim SY, Davidson SM, Paramanathan AJ, Smith CC, Yellon DM, Hausenloy DJ. The novel adipocytokine visfatin exerts direct cardioprotective effects. J Cell Mol Med. 2008;12(4): 1395-1403.
177. O'Dowd BF, Heiber M, Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene. 1993;136(1-2):355-360.
178. Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 1998;251(2):471-476.
179. Kawamata Y, Habata Y, Fukusumi S, et al. Molecular properties of apelin: tissue distribution and receptor binding. Biochim Biophys Acta. 2001;1538(2-3):162-171.
180. Lee DK, Saldivia VR, Nguyen T, Cheng R, George SR, O'Dowd BF. Modification of the terminal residue of apelin-13 antagonizes its hypotensive action. Endocrinology. 2005;146(1):231-236.
181. Lee DK, George SR, O'Dowd BF. Unravelling the roles of the apelin system: prospective therapeutic applications in heart failure and obesity. Trends Pharmacol Sci. 2006;27(4):190-194.
182. Castan-Laurell I, Vitkova M, Daviaud D, et al. Effect of hypocaloric diet-induced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ. Eur J Endocrinol. 2008;158(6):905-910.
183. Kleinz MJ, Skepper JN, Davenport AP. Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells. Regul Pept. 2005;126(3):233-240.
184. Kleinz MJ, Davenport AP. Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Regul Pept. 2004;118(3): 119-125.
185. Boucher J, Masri B, Daviaud D, et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology. 2005;146(4):1764-1771.
186. Kadoglou NP, Lampropoulos S, Kapelouzou A, et al. Serum levels of apelin and ghrelin in patients with acute coronary syndromes and established coronary artery disease-kozani study. Transl Res. 2010;155(5):238-246.
187. Weir RA, Chong KS, Dalzell J.R., et al. Plasma apelin concentration is depressed following acute myocardial infarction in man. Eur J Heart Fail. 2009;11(6):551-558.
188. Ye J, Ni P, Kang L, Xu B. Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction. J Biomed Res. 2012;26(6):400-409.
189. Kuklinska AM, Sobkowicz B, Sawicki R, et al. Apelin: a novel marker for the patients with first ST-elevation myocardial infarction. Heart Vessels. 2010;25(5):363-367.
190. Tycinska AM, Sobkowicz B, Mroczko B, et al. The value of apelin-36 and brain natriuretic peptide measurements in patients with first ST-elevation myocardial infarction. Clin Chim Acta. 2010;411(23-24):2014-2018.
191. Tasci I, Dogru T, Naharci I, et al. Plasma apelin is lower in patients with elevated LDL-cholesterol. Exp Clin Endocrinol Diabetes. 2007;115(7):428-432.
192. Sonmez A, Celebi G, Erdem G, et al. Plasma apelin and ADMA levels in patients with essential hypertension. Clin Exp Hypertens. 2010;32(3):179-183.
193. Rittig K, Hildebrandt U, Thamer C, et al. Apelin serum levels are not associated with early atherosclerosis or fat distribution in young subjects with increased risk for type 2 diabetes. Exp Clin Endocrinol Diabetes. 2011;119(6):358-361.
194. Pitkin SL, Maguire JJ, Kuc RE, Davenport AP. Modulation of the apelin/APJ system in heart failure and atherosclerosis in man. Br J Pharmacol. 2010;160(7):1785-1795.
195. Li F, Li L, Qin X, et al. Apelin-induced vascular smooth muscle cell proliferation: the regulation of cyclin D1. Front Biosci. 2008;13:3786-3792.
196. Kojima Y, Kundu RK, Cox CM, et al. Upregulation of the apelin- APJ pathway promotes neointima formation in the carotid ligation model in mouse. Cardiovasc Res. 2010;87(1):156-165.
197. Lu Y, Zhu X, Liang GX, et al. Apelin-APJ induces ICAM-1, VCAM-1 and MCP-1 expression via NF-kappaB/JNK signal pathway in human umbilical vein endothelial cells. Amino Acids. 2012;43(5):2125-2136.
198. Hashimoto T, Kihara M, Imai N, et al. Requirement of apelin- apelin receptor system for oxidative stress-linked atherosclerosis. Am J Pathol. 2007;171(5):1705-1712.
199. Chun HJ, Ali ZA, Kojima Y, et al. Apelin signaling antagonizes ANG II effects in mouse models of atherosclerosis. J Clin Invest. 2008;118(10):3343-3354.
200. Shan PF, Lu Y, Cui RR, Jiang Y, Yuan LQ, Liao EY. Apelin attenuates the osteoblastic differentiation of vascular smooth muscle cells. PLoS One. 2011;6(3):e17938.
201. Tatemoto K, Takayama K, Zou MX, et al. The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism. Regul Pept. 2001;99(2-3):87-92.
202. Ishida J, Hashimoto T, Hashimoto Y, et al. Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensintype 1 receptor in blood pressure in vivo. J Biol Chem. 2004; 279(25):26274-26279.
203. Cheng X, Cheng XS, Pang CC. Venous dilator effect of apelin, an endogenous peptide ligand for the orphan APJ receptor, in conscious rats. Eur J Pharmacol. 2003;470(3):171-175.
204. Ashley EA, Powers J, Chen M, et al. The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc Res. 2005;65(1):73-82.
205. Zhang Q, Yao F, Raizada MK, O'Rourke ST, Sun C. Apelin gene transfer into the rostral ventrolateral medulla induces chronic blood pressure elevation in normotensive rats. Circ Res. 2009;104(12):1421-1428.
206. Nagano K, Ishida J, Unno M, Matsukura T, Fukamizu A. Apelin elevates blood pressure in ICR mice with L-NAME-induced endothelial dysfunction. Mol Med Rep. 2013;7(5):1371-1375.
207. Jia YX, Lu ZF, Zhang J, et al. Apelin activates L-arginine/nitric oxide synthase/nitric oxide pathway in rat aortas. Peptides. 2007;28(10):2023-2039.
208. Kagiyama S, Fukuhara M, Matsumura K, Lin Y, Fujii K, Iida M. Central and peripheral cardiovascular actions of apelin in conscious rats. Regul Pept. 2005;125(1-3):55-59.
209. Seyedabadi M, Goodchild AK, Pilowsky PM. Site-specific effects of apelin-13 in the rat medulla oblongata on arterial pressure and respiration. Auton Neurosci. 2002;101(1-2):32-38.
210. Iwanaga Y, Kihara Y, Takenaka H, Kita T. Down-regulation of cardiac apelin system in hypertrophied and failing hearts: possible role of angiotensin II-angiotensin type 1 receptor system. J Mol Cell Cardiol. 2006;41(5):798-806.
211. Ronkainen VP, Ronkainen JJ, Hanninen SL, et al. Hypoxia inducible factor regulates the cardiac expression and secretion of apelin. FASEB J. 2007;21(8):1821-1830.
212. Atluri P, Morine KJ, Liao GP, et al. Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression. Cell Mol Biol Lett. 2007;12(1):127-138.
213. Zhang J, Ren CX, Qi YF, et al. Exercise training promotes expression of apelin and APJ of cardiovascular tissues in spontaneously hypertensive rats. Life Sci. 2006;79(12): 1153-1159.
214. Higuchi K, Masaki T, Gotoh K, et al. Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice. Endocrinology. 2007;148(6):2690-2697.
215. Berry MF, Pirolli TJ, Jayasankar V, et al. Apelin has in vivo inotropic effects on normal and failing hearts. Circulation. 2004;110(11 suppl 1):II187-II193.
216. Szokodi I, Tavi P, Foldes G, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res. 2002;91(5):434-440.
217. Dai T, Ramirez-Correa G, Gao WD. Apelin increases contractility in failing cardiac muscle. Eur J Pharmacol. 2006;553(1-3): 222-228.
218. Chong KS, Gardner RS, Morton JJ, Ashley EA, McDonagh TA. Plasma concentrations of the novel peptide apelin are decreased in patients with chronic heart failure. Eur J Heart Fail. 2006; 8(4):355-360.
219. Ellinor PT, Low AF, Macrae CA. Reduced apelin levels in lone atrial fibrillation. Eur Heart J. 2006;27(2):222-226.
220. Francia P, Salvati A, Balla C, et al. Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin. Eur J Heart Fail. 2007;9(3):306-309.
221. de Souza Batista CM, Yang RZ, Lee MJ, et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes. 2007;56(6):1655-1661.
222. Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes Res Clin Pract. 2010;88(1):29-33.
223. Yang RZ, Lee MJ, Hu H, et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab. 2006;290(6):E1253-E1261.
224. Shang FJ, Wang JP, Liu XT, et al. Serum omentin-1 levels are inversely associated with the presence and severity of coronary artery disease in patients with metabolic syndrome. Biomarkers. 2011;16(8):657-662.
225. Shibata R, Ouchi N, Kikuchi R, et al. Circulating omentin is associated with coronary artery disease in men. Atherosclerosis. 2011;219(2):811-814.
226. Zhong X, Zhang HY, Tan H, et al. Association of serum omentin-1 levels with coronary artery disease. Acta Pharmacol Sin. 2011;32(7):873-878.
227. Liu R, Wang X, Bu P. Omentin-1 is associated with carotid atherosclerosis in patients with metabolic syndrome. Diabetes Res Clin Pract. 2011;93(1):21-25.
228. Duan XY, Xie PL, Ma YL, Tang SY. Omentin inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells through the Pi3k/Akt pathway. Amino Acids. 2011;41(5): 1223-1231.
229. Yoo HJ, Hwang SY, Hong HC, et al. Association of circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes. Cardiovasc Diabetol. 2011;10103.
230. Yamawaki H, Tsubaki N, Mukohda M, Okada M, Hara Y. Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem Biophys Res Commun. 2010;393(4): 668-672.
231. Tan BK, Adya R, Randeva HS. Omentin: a novel link between inflammation, diabesity, and cardiovascular disease. Trends Cardiovasc Med. 2010;20(5):143-148.
232. Greulich S, Chen WJ, Maxhera B, et al. Cardioprotective properties of omentin-1 in type 2 diabetes: evidence from clinical and in vitro studies. PLoS One. 2013;8(3):e59697.
233. Kloting N, Berndt J, Kralisch S, et al. Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun. 2006;339(1):430-436.
234. Cho JK, Han TK, Kang HS. Combined effects of body mass index and cardio/respiratory fitness on serum vaspin concentrations in Korean young men. Eur J Appl Physiol. 2010;108(2): 347-353.
235. Youn BS, Kloting N, Kratzsch J, et al. Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes. 2008; 57(2):372-377.
236. Ye Y, Hou XH, Pan XP, Lu JX, Jia WP. Serum vaspin level in relation to postprandial plasma glucose concentration in subjects with diabetes. Chin Med J (Engl). 2009;122(21):2530-2533.
237. Lago F, Dieguez C, Gomez-Reino J, Gualillo O. The emerging role of adipokines as mediators of inflammation and immune responses. Cytokine Growth Factor Rev. 2007;18(3-4):313-325.
238. Hida K, Wada J, Eguchi J, et al. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci USA. 2005;102(30): 10610-10615.
239. Seeger J, Ziegelmeier M, Bachmann A, et al. Serum levels of the adipokine vaspin in relation to metabolic and renal parameters. J Clin Endocrinol Metab. 2008;93(1):247-251.
240. Li HL, Peng WH, Cui ST, et al. Vaspin plasma concentrations and mRNA expressions in patients with stable and unstable angina pectoris. Clin Chem Lab Med. 2011;49(9):1547-1554.
241. Aust G, Richter O, Rohm S, et al. Vaspin serum concentrations in patients with carotid stenosis. Atherosclerosis. 2009;204(1): 262-266.
242. Jung CH, Lee WJ, Hwang JY, et al. Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway. Biochem Biophys Res Commun. 2011;413(2):264-269.
243. Wada J. Vaspin. A novel serpin with insulin-sensitizing effects. Expert Opin Investig Drugs. 2008;17(3):327-333.
244. Phalitakul S, Okada M, Hara Y, Yamawaki H. Vaspin prevents TNF-alpha-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-kappaB and PKCtheta activation in cultured rat vascular smooth muscle cells. Pharmacol Res. 2011;64(5):493-500.
245. Kotnik P, Fischer-Posovszky P, Wabitsch M. Rbp4: a controversial adipokine. Eur J Endocrinol. 2011;165(5):703-711.
246. Colantuoni V, Romano V, Bensi G, et al. Cloning and sequencing of a full length cDNA coding for human retinol-binding protein. Nucleic Acids Res. 1983;11(22):7769-7776.
247. Blaner WS. Retinol-binding protein: the serum transport protein for vitamin a. Endocr Rev. 1989;10(3):308-316.
248. Tsutsumi C, Okuno M, Tannous L, et al. Retinoids and retinoidbinding protein expression in rat adipocytes. J Biol Chem. 1992; 267(3):1805-1810.
249. Zovich DC, Orologa A, Okuno M, et al. Differentiationdependent expression of retinoid-binding proteins in BFC-1 beta adipocytes. J Biol Chem. 1992;267(20):13884-13889.
250. Kelly KR, Kashyap SR, O'Leary VB, Major J, Schauer PR, Kirwan JP. Retinol-binding protein 4 (RBP4) protein expression is increased in omental adipose tissue of severely obese patients. Obesity (Silver Spring). 2010;18(4):663-666.
251. Kloting N, Graham TE, Berndt J, et al. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab. 2007;6(1):79-87.
252. Erikstrup C, Mortensen OH, Nielsen AR, et al. RBP-to-retinol ratio, but not total RBP, is elevated in patients with type 2 diabetes. Diabetes Obes Metab. 2009;11(3):204-212.
253. Sivaprasadarao A, Findlay JB. The interaction of retinol-binding protein with its plasma-membrane receptor. Biochem J. 1988; 255(2):561-569.
254. Matarese V, Lodish HF. Specific uptake of retinol-binding protein by variant F9 cell lines. J Biol Chem. 1993;268(25): 18859-18865.
255. Kawaguchi R, Yu J, Honda J, et al. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science. 2007;315(5813):820-825.
256. Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996;10(9):940-954.
257. Yang Q, Graham TE, Mody N, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005;436(7049):356-362.
258. Graham TE, Yang Q, Bluher M, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med. 2006;354(24):2552-2563.
259. Balagopal P, Graham TE, Kahn BB, Altomare A, Funanage V, George D. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. J Clin Endocrinol Metab. 2007;92(5): 1971-1974.
260. Hermsdorff HH, Zulet MA, Puchau B, Martinez JA. Central adiposity rather than total adiposity measurements are specifically involved in the inflammatory status from healthy young adults. Inflammation. 2011;34(3):161-170.
261. Haider DG, Schindler K, Prager G, et al. Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2007;92(3):1168-1171.
262. Janke J, Engeli S, Boschmann M, et al. Retinol-binding protein 4 in human obesity. Diabetes. 2006;55(10):2805-2810.
263. Lee JW, Lee HR, Shim JY, Im JA, Lee DC. Abdominal visceral fat reduction is associated with favorable changes of serum retinol binding protein-4 in nondiabetic subjects. Endocr J. 2008; 55(5):811-818.
264. Vitkova M, Klimcakova E, Kovacikova M, et al. Plasma levels and adipose tissue messenger ribonucleic acid expression of retinol-binding protein 4 are reduced during calorie restriction in obese subjects but are not related to diet-induced changes in insulin sensitivity. J Clin Endocrinol Metab. 2007;92(6): 2330-2335.
265. Cho YM, Youn BS, Lee H, et al. Plasma retinol-binding protein- 4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes. Diabetes Care. 2006; 29(11):2457-2461.
266. Kloting N, Fasshauer M, Dietrich A, et al. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010;299(3):E506-E515.
267. Ribel-Madsen R, Friedrichsen M, Vaag A, Poulsen P. Retinolbinding protein 4 in twins: regulatory mechanisms and impact of circulating and tissue expression levels on insulin secretion and action. Diabetes. 2009;58(1):54-60.
268. Yao-Borengasser A, Varma V, Bodles AM, et al. Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone. J Clin Endocrinol Metab. 2007;92(7):2590-2597.
269. Christou GA, Tselepis AD, Kiortsis DN. The metabolic role of retinol binding protein 4: an update. Horm Metab Res. 2012; 44(1):6-14.
270. Ingelsson E, Sundstrom J, Melhus H, et al. Circulating retinolbinding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly. Atherosclerosis. 2009;206(1): 239-244.
271. Lim S, Yoon JW, Choi SH, et al. Combined impact of adiponectin and retinol-binding protein 4 on metabolic syndrome in elderly people: the Korean longitudinal study on health and aging. Obesity (Silver Spring). 2010;18(4):826-832.
272. Makino S, Fujiwara M, Suzukawa K, et al. Visceral obesity is associated with the metabolic syndrome and elevated plasma retinol binding protein-4 level in obstructive sleep apnea syndrome. Horm Metab Res. 2009;41(3):221-226.
273. Qi Q, Yu Z, Ye X, et al. Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people. J Clin Endocrinol Metab. 2007;92(12):4827-4834.
274. Lin CC, Lai MM, Li TC, et al. Relationship between serum retinol-binding protein 4 and visfatin and the metabolic syndrome. Diabetes Res Clin Pract. 2009;85(1):24-29.
275. Park SE, Kim DH, Lee JH, et al. Retinol-binding protein-4 is associated with endothelial dysfunction in adults with newly diagnosed type 2 diabetes mellitus. Atherosclerosis. 2009; 204(1):23-25.
276. Ingelsson E, Lind L. Circulating retinol-binding protein 4 and subclinical cardiovascular disease in the elderly. Diabetes Care. 2009;32(4):733-735.
277. Solini A, Santini E, Madec S, Rossi C, Muscelli E. Retinolbinding protein-4 in women with untreated essential hypertension. Am J Hypertens. 2009;22(9):1001-1006.
278. Bobbert T, Raila J, Schwarz F, et al. Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness. Atherosclerosis. 2010;213(2):549-551.
279. Cabre A, Lazaro I, Girona J, et al. Retinol-binding protein 4 as a plasma biomarker of renal dysfunction and cardiovascular disease in type 2 diabetes. J Intern Med. 2007;262(4):496-503.
280. Mallat Z, Simon T, Benessiano J, et al. Retinol-binding protein 4 and prediction of incident coronary events in healthy men and women. J Clin Endocrinol Metab. 2009;94(1):255-260.
281. Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51(2):679-689.
282. Mendez-Sanchez N, Arrese M, Zamora-Valdes D, Uribe M. Current concepts in the pathogenesis of nonalcoholic fatty liver disease. Liver Int. 2007;27(4):423-433.
283. Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001; 50(8):1844-1850.
284. Tonjes A, Bluher M, Stumvoll M. Retinol-binding protein 4 and new adipocytokines in nonalcoholic fatty liver disease. Curr Pharm Des. 2010;16(17):1921-1928.
285. Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism. 2011;60(3): 313-326.
286. Wree A, Kahraman A, Gerken G, Canbay A. Obesity affects the liver-the link between adipocytes and hepatocytes. Digestion. 2011;83(1-2):124-133.
287. Tilg H. The role of cytokines in non-alcoholic fatty liver disease. Dig Dis. 2010;28(1):179-185.
288. Polyzos SA, Kountouras J, Zavos C, Tsiaousi E. The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease. Diabetes Obes Metab. 2010;12(5):365-383.
289. Chitturi S, Farrell G, Frost L, et al. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? Hepatology. 2002;36(2):403-409.
290. Pagano C, Soardo G, Pilon C, et al. Increased serum resistin in nonalcoholic fatty liver disease is related to liver disease severity and not to insulin resistance. J Clin Endocrinol Metab. 2006; 91(3):1081-1086.
291. Perseghin G, Bonfanti R, Magni S, et al. Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease. Am J Physiol Endocrinol Metab. 2006;291(4): E697-E703.
292. Schina M, Koskinas J, Tiniakos D, et al. Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease. Hepatol Res. 2009;39(10):972-928.
293. Stefan N, Hennige AM, Staiger H, et al. High circulating retinolbinding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care. 2007;30(5):1173-1178.
294. Alkhouri N, Lopez R, Berk M, Feldstein AE. Serum retinolbinding protein 4 levels in patients with nonalcoholic fatty liver disease. J Clin Gastroenterol. 2009;43(10):985-989.
295. Jarrar MH, Baranova A, Collantes R, et al. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2008;27(5):412-421.