Expression Of MMP-1, TIMP-1 And ICAM-1 Induced By Visfatin In Human Umbilical Vein Endothelial Cells

Background:As we know that atherosclerosis is the most important risk factor of cardiovascular and cardio-cerebrovascular disease. With the improvement of living standards and changing of eating habits, the incidence of obesity and obesity-related diseases such as diabetes, hypertension and hyperlipemia has gradually increased, and these diseases affect on the formation and development of atherosclerosis through various mechanisms. Recent studies have shown that several cytokines secreted by excess adipose tissue of obesity play an important role in the occurrence of atherosclerosis.Visfatin is the most recently identified adipocytokine(known previously as pre-B cell colony enhancing factor, PBEF).Visfatin has not only associated with a variety of inflammatory diseases,but also can regulate the synthesis and secretion of inflammatory cytokine,stimulate the monoeyte releasing intereellular adhesion moleeule-1 and the endothelium releasing vascular endothelium growth factor. It has been found that visfatin expressed in carotid endarterectomy specimens and coronary artery plaques. This indicates that visfatin is not only an cytokine but also interact with atherosclerosis. MMP-1,TIMP-1 and ICAM-1 play an important role in the inflammation-induced endothelial cell injury.Objective:To investigate the mechanism of artherosclerosis and plaque disurptioninduced by dysfunction of vascular endothelial cell with visfatin in different concentrations, we evaluate the effect of visfatin on the genetic expression of MMP-1,TIMP-1 and ICAM-1 in human vascular endothelium.Method:HUVECs were incubated in vitro and treated with visfatin in 100ng/ml,200ng/ml,400ng/ml,800ng/ml levels for 24 hours respectively.Then total cellular RNA was extracted by Trizol method and the expression of MMP-1,TIMP-1 and ICAM-1 were detected in mRNA levels using RT-PCR method.Results:(1)Visfatin can increase the expression of MMP-1 mRNA significantly in a dose-dependent manner.(2)Visfatin can reduce the expression of TIMP-1 mRNA significantly in a dose-dependent manner,and the ratio of MMP-1/TIMP-1 increased gradually with the increase of visfatin.(3)Visfatin can increase the expression of ICAM-1 mRNA significantly in a dose-dependent manner.Conclusion:(1)The endothelium stimulated with visfatin can increase the expression of MMP-1 mRNA in a dose-dependent manner. And visfatin can down regulate the expression of TIMP-1 mRNA and result in the proportional imbalance of MMP-1/TIMP-1,which break the extracellular matrix synthesis and degradation balance finally.(2)The endothelium stimulated with visfatin can increase the expression of ICAM-1 mRNA in a dose-dependent manner.(3) Visfatin may be involved in the artery atherosclerotic disease through affecting the expression of MMP-1, TIMP-1 and ICAM-1 in human vascular endothelial cells.