The mRNA Expression and Circulating Levels of Visfatin and Their Correlation with Coronary Artery Disease Severity and 25-Hydroxyvitamin D

Abstract

It is evident that coronary artery disease (CAD) is closely associated with abnormal glucose and lipid metabolism. Notably, dysregulation of inflammatory pathways and immune system also contribute to CAD development. Recently, it has been suggested that visfatin, a proinflammatory adipocytokine, may be involved in several inflammatory and metabolic diseases. In this study, we evaluated the serum visfatin levels and its mRNA expression in peripheral blood mononuclear cells (PBMCs) from CAD patients compared with control subjects. We also studied the correlation between visfatin gene expression and serum levels with clinical and metabolic parameters. This study was conducted on 56 male patients with CAD confirmed by angiography and 30 healthy men as controls. CAD severity was determined based on the number of vessels. Study of gene expression in PBMCs was performed using real time-PCR, and serum levels of visfatin and 25-hydroxyvitamin D were measured by ELISA. We found that serum visfatin levels and its gene expression in PBMCs were increased in patients with CAD compared with the control group (p=0.027 and p=0.016, respectively). Also, visfatin gene expression was positively correlated with visfatin levels and both these variables had a strong positive correlation with the severity of CAD. It appears that elevated mRNA expression and circulating level of visfatin might be of relevance to the pathogenesis and severity of CAD. However, further studies are necessary to better clarify the associations between visfatin and CAD.

Key words

peripheral blood mononuclear cells - adipokines - atherosclerosis - cardiovascular disease - visfatin

^* These authors contributed equally to this work

• References

• 1 Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-1695
• 2 Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol 2009; 27: 165-197
• 3 Romacho T, Sanchez-Ferrer CF, Peiro C. Visfatin/nampt: An adipokine with cardiovascular impact. Mediators Inflamm 2013; 946427
• 4 Zhang H, Cui J, Zhang C. Emerging role of adipokines as mediators in atherosclerosis. World J Cardiol 2010; 2: 370-376
• 5 Lago F, Dieguez C, Gomez-Reino J, Gualillo O. Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol 2007; 3: 716-724
• 6 Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 2005; 307: 426-430
• 7 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: 1431-1437
• 8 Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F. Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol 2002; 32: 3225-3234
• 9 Liu SW, Qiao SB, Yuan JS, Liu DQ. Visfatin stimulates production of monocyte chemotactic protein-1 and interleukin-6 in human vein umbilical endothelial cells. Horm Metab Res 2009; 41: 281-286
• 10 Laudes M, Oberhauser F, Schulte DM, Freude S, Bilkovski R, Mauer J, Rappl G, Abken H, Hahn M, Schulz O, Krone W. Visfatin/PBEF/Nampt and resistin expressions in circulating blood monocytes are differentially related to obesity and type 2 diabetes in humans. Horm Metab Res 2010; 42: 268-273
• 11 Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2006; 91: 295-299
• 12 Filippatos TD, Derdemezis CS, Gazi IF, Lagos K, Kiortsis DN, Tselepis AD, Elisaf MS. Increased plasma visfatin levels in subjects with the metabolic syndrome. Eur J Clin Invest 2008; 38: 71-72
• 13 Dahl TB, Yndestad A, Skjelland M, Oie E, Dahl A, Michelsen A, Damas JK, Tunheim SH, Ueland T, Smith C, Bendz B, Tonstad S, Gullestad L, Froland SS, Krohg-Sorensen K, Russell D, Aukrust P, Halvorsen B. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. Circulation 2007; 115: 972-980
• 14 Choi YJ, Choi SE, Ha ES, Kang Y, Han SJ, Kim DJ, Lee KW, Kim HJ. Extracellular visfatin activates gluconeogenesis in hepg2 cells through the classical pka/creb-dependent pathway. Horm Metab Res 2014; 46: 233-239
• 15 Nencioni A, da Silva RF, Fraga-Silva RA, Steffens S, Fabre M, Bauer I, Caffa I, Magnone M, Sociali G, Quercioli A, Pelli G, Lenglet S, Galan K, Burger F, Vazquez Calvo S, Bertolotto M, Bruzzone S, Ballestrero A, Patrone F, Dallegri F, Santos RA, Stergiopulos N, Mach F, Vuilleumier N, Montecucco F. Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice. Thromb Haemost 2014; 111: 308-322
• 16 Zhou F, Pan Y, Huang Z, Jia Y, Zhao X, Chen Y, Diao J, Wan Q, Cui X. Visfatin induces cholesterol accumulation in macrophages through up-regulation of scavenger receptor-A and CD36. Cell Stress Chaperones 2013; 18: 643-652
• 17 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: 202-207
• 18 Cheng KH, Chu CS, Lee KT, Lin TH, Hsieh CC, Chiu CC, Voon WC, Sheu SH, Lai WT. Adipocytokines and proinflammatory mediators from abdominal and epicardial adipose tissue in patients with coronary artery disease. Int J Obes (Lond) 2008; 32: 268-274
• 19 Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008; 3: 1101-1108
• 20 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: 878-884
• 21 Scotece M, Conde J, Gomez R, Lopez V, Pino J, Gonzalez A, Lago F, Gomez-Reino JJ, Gualillo O. Role of adipokines in atherosclerosis: Interferences with cardiovascular complications in rheumatic diseases. Mediators Inflamm 2012; 125458
• 22 Hector J, Schwarzloh B, Goehring J, Strate TG, Hess UF, Deuretzbacher G, Hansen-Algenstaedt N, Beil FU, Algenstaedt P. TNF-alpha alters visfatin and adiponectin levels in human fat. Horm Metab Res 2007; 39: 250-255
• 23 Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 2007; 178: 1748-1758
• 24 Kadoglou NP, Saile N, Moumtzouoglou A, Kapelouzou A, Tsanikidis H, Vitta I, Karkos C, Karayannacos PE, Gerasimidis T, Liapis CD. Visfatin (nampt) and ghrelin as novel markers of carotid atherosclerosis in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 2010; 118: 75-80
• 25 Kadoglou NP, Gkontopoulos A, Kapelouzou A, Fotiadis G, Theofilogiannakos EK, Kottas G, Lampropoulos S. Serum levels of vaspin and visfatin in patients with coronary artery disease-Kozani study. Clin Chim Acta 2011; 412: 48-52
• 26 Choi KM, Lee JS, Kim EJ, Baik SH, Seo HS, Choi DS, Oh DJ, Park CG. Implication of lipocalin-2 and visfatin levels in patients with coronary heart disease. Eur J Endocrinol 2008; 158: 203-207
• 27 Masud R, Shameer K, Dhar A, Ding K, Kullo IJ. Gene expression profiling of peripheral blood mononuclear cells in the setting of peripheral arterial disease. J Clin Bioinforma 2012; 2: 6-10
• 28 Seow KM, Hwang JL, Wang PH, Ho LT, Juan CC. Expression of visfatin mRNA in peripheral blood mononuclear cells is not correlated with visfatin mRNA in omental adipose tissue in women with polycystic ovary syndrome. Hum Reprod 2011; 26: 2869-2873
• 29 Tsiotra PC, Tsigos C, Yfanti E, Anastasiou E, Vikentiou M, Psarra K, Papasteriades C, Raptis SA. Visfatin, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women. Horm Metab Res 2007; 39: 758-763
• 30 Friebe D, Neef M, Kratzsch J, Erbs S, Dittrich K, Garten A, Petzold-Quinque S, Bluher S, Reinehr T, Stumvoll M, Bluher M, Kiess W, Korner A. Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans. Diabetologia 2011; 54: 1200-1211
• 31 Curat CA, Wegner V, Sengenes C, Miranville A, Tonus C, Busse R, Bouloumie A. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 2006; 49: 744-747
• 32 Pittelli M, Cavone L, Lapucci A, Oteri C, Felici R, Niccolai E, Amedei A, Chiarugi A. Nicotinamide phosphoribosyltransferase (NAMPT) activity is essential for survival of resting lymphocytes. Immunol Cell Biol 2014; 92: 191-199
• 33 Reddy Vanga S, Good M, Howard PA, Vacek JL. Role of vitamin D in cardiovascular health. Am J Cardiol 2010; 106: 798-805
• 34 Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). Am J Cardiol 2008; 102: 1540-1544
• 35 Li YC, Kong J, Wei M, Chen Z-F, Liu SQ, Cao L-P. 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002; 110: 229-238
• 36 Muscogiuri G, Sorice GP, Prioletta A, Policola C, Della Casa S, Pontecorvi A, Giaccari A. 25-Hydroxyvitamin D concentration correlates with insulin-sensitivity and BMI in obesity. Obesity (Silver Spring) 2010; 18: 1906-1910
• 37 Heikkinen AM, Tuppurainen MT, Niskanen L, Komulainen M, Penttila I, Saarikoski S. Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy. Eur J Endocrinol 1997; 137: 495-502
• 38 Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 2012; 188: 2127-2135
• 39 Mayi TH, Duhem C, Copin C, Bouhlel MA, Rigamonti E, Pattou F, Staels B, Chinetti-Gbaguidi G. Visfatin is induced by peroxisome proliferator-activated receptor gamma in human macrophages. FEBS J 2010; 16: 3308-3320
• 40 Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, Proctor BM, Petty M, Chen Z, Schechtman KB, Bernal-Mizrachi L, Bernal-Mizrachi C. 1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation 2009; 120: 687-698
• 41 Tokunaga A, Miura A, Okauchi Y, Segawa K, Fukuhara A, Okita K, Takahashi M, Funahashi T, Miyagawa J, Shimomura I, Yamagata K. The -1535 promoter variant of the visfatin gene is associated with serum triglyceride and HDL-cholesterol levels in Japanese subjects. Endocr J 2008; 55: 205-512