Visceral Fat Levels And Coronary Heart Disease

Part One Effects of visfatin on production of monocyte mhemotactic protein-1 and interleukin-6 in Human Vein Umbilical Endothelial CellsObjective and Backgroud:Visfatin is a novel adipocytokine affecting insulin resistance by binding to the insulin receptor and considered a new proinflammatory adipocytokine. Monocyte chemotactic protein-1(MCP-1) and interleukin-6(IL-6) are importantly inflammatory cytokines involved in atherosclerosis.Whether visfatin stimulates MCP-1 and IL-6 production in human endothelial cells and what signaling pathways are involved in are not known.Methods:Cultured human umbilical vein endothelial cells(HUVEC) were treated with different doses and durations of visfatin.Furthermore,HUVEC were pretreated with wortmannin,a phosphatidylinositol-3-kinase(PI3K) inhibitors,PD98059,an extracellular regulated kinase kinase(ERK) inhibitor,SB203580,a mitogen-activated protein kinase(p38 MAPK) inhibitors and hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester(HNMPA-(AM)3),a specific inhibitor of insulin receptor (IR) followed by visfatin(100ng/mL) treatment.Enzyme-linked immunosorbent assay (ELISA) was used for measuring MCP-1 and IL-6 production in HUVEC.Real-time quantitative reverse-transcription polymerase chain reaction(Real-time-PCR) was used for determining MCP-1 and IL-6 mRNA expression.Results:In the present study,we demonstrated that visfatin significantly and dose-and time-dependently up-regulated protein production of MCP-1 and IL-6 in HUVEC,which the dose of 500ng/mL or 48 hours duration of visfatin treatment had the maximal effect. We therefore found visfatin-induced MCP-1 and IL-6 production and gene expression in HUVEC were diminished by wortmannin,PD98059 and SB203580.Furthermore, HNMPA-(AM)3 also reduced visfatin-mediated MCP-1 and IL-6 production and gene expression in HUVEC.Conclusions:Our findings suggest that visfatin might induce endothelial MCP-1 and IL-6 production in HUVEC with dose- and time-dependently manner.This dysregulation appears to be mediated in part via p38,PI3K and ERK signaling pathways,as well as insulin receptor pathway. Part Two Association between Plasma Visfatin Levels and Inflammation, Atherosclerosis,and Acute Coronary Syndromes in HumansObjective and Backgroud:Visfatin is a new cytokine that act as an insulin analog on the insulin receptor and may link to obesity and insulin resistance.It was recently shown visfatin play a role in inflammation,dysfunction of endothelium and plaque destabilization.However,the role of visfatin in atherosclerosis remains to be elucidated. We sought to assess whether plasma visfatin level can be independently associated with inflammation,atherosclerosis,and acute coronary syndromes(ACS).Mathods:Two hundred fifty-three patients undergoing coronary angiography were divided into three subgroups:stable angina pectoris(SAP)(n=102),ACS(n=100) and the control patients(n=51).Clinical and biochemical characteristics were collected.The plasma samples were thawed and analyzed for circulating visfatin,monocyte chemoattractant protein 1(MCP-1),interleukin-6(IL-6) by enzyme-linked immunosorbent assay(ELISA).The levels of high-sensitivity C-reactive protein(hs-CRP) were determined by immunoturbidometry,The association of visfatin with risk factors, inflammation and atherosclerosis,as well as ACS were determined.Results:Plasma visfatin levels were significantly higher in SAP(12.0(9.7,15.5)pg/mL, p＜0.05) and ACS(13.4(11.1,15.9) pg/mL,p＜0.01)compared with control patients (10.2(8.7,12.8) pg/mL).Subgroup analysis in all patients with coronary artery disease confirmed that plasma visfatin level were not significantly difference in with or without diabetes,with or without hyperlidimia,with or without obesity.Multiple regression analysis demonstrated that plasma visfatin levels positively correlated with MCP-1,IL-6 and FPG(βvalue for MCP-1,IL-6,FPG were 0.0029,0.337,0.104,respectively). Logsitic regression analysis demonstrated that plasma visfatin levels were associated with SAP(odds ratio[OR][95%confidence interval],for in the second,third and fourth quartiles were 1.74[0.96 to 2.69],1.54[0.85 to 2.28]and 1.84[0.98 to 2.87], respectively),ACS(ORs for in the second,third and fourth quartiles were 2.56[1.57 to 3.34],4.61[1.94 to 10.96]and 6.52[2.34 to 18.12],respectively)following adjustment for established risk factors and other inflammatory factors. Conclusions:Plasma visfatin levels are significantly associated with CAD,particularly ACS,independent of well-known CAD risk factors.