The Effects Of Visfatin On Vascular Complications In Diabetes Mellitus And Its Mechanism

Objective:To investigate the effects of visfatin on expression of MCP-1 and ICAM-1 in vascular endothelial cells under high glucose condition and its mechanism.Methods:Human umbilical vein endothelial cell (HUVEC) were cultured in vitro and divided into 3 groups: control group (0mmol/L glucose); normal glucose group (5.5mmol/L glucose); high glucose group (25mmol/L glucose), and HUVEC were incubated with human recombinant visfatin in various concentrations (0ng/ml, 10ng/ml, 50ng/ml, 100ng/ml) for 24 hours. Another part of HUVEC incubated with 100ng/ml visfatin and glucose in various concentrations (0mmol/L, 5.5mmol/L, 25mmol/L) for 24 hours with SB203580, p38 mitogen-activated protein kinase (p38MAPK) signal pathway inhibitor, pretreatment for 30 minutes. Expression of MCP-1 and ICAM-1 proteins in HUVEC was examined by enzyme-linked immunosorbent assay (ELISA),expression of p38MAPK mRNA in HUVEC was determined by reverse transcription-polymerase chain reaction (RT-PCR) and the proteins of phosphor-p38MAPK in HUVEC was analyzed by Western blot.Results:Expression of p38MAPK mRNA, phosphor-p38MAPK, MCP-1 and ICAM-1 in HUVEC were significantly promoted by visfatin with dose-dependent response in control group and normal glucose group (P<0.01). Under high glucose condition (25mmol/L), visfatin had a synergetic effect on stimulating the expression of p38MAPK mRNA and the proteins of phosphor-p38MAPK in HUVEC and concentrations of MCP-1 and ICAM-1 released from HUVEC (P<0.05). Under these glucose conditions, the effects of visfatin on expression of the proteins of phosphor-p38MAPK and MCP-1 and ICAM-1 were weakened significantly by SB203580, a specific inhibitor of p38MAPK pathway (P<0.01).Conclusion:Visfatin, which has recently been indentified as a novel visceral adipokine, is a vascular pro-inflammatory cytokines. Our data provide the evidence that visfatin can increase the expression of the inflammatory MCP-1 and ICAM-1 via p38MAPK pathways and High glucose can enhance the effects that visfatin induces the expression of MCP-1 and ICAM-1 in HUVEC, which accelerates dysfunction of vascular endothelial cell.