Leptin-induced vascular smooth muscle cell proliferation via regulating cell cycle, activating ERK1/2 and NF-kappaB.

Leptin is a peptide hormone primarily involved in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is one of the risk factors for cardiovascular diseases including atherosclerosis and hypertension. Vascular smooth muscle cells (VSMCs) play a vital role in arterial intimal thickening and vascular remodeling. In this study, we investigated the effect of leptin on VSMC cell-cycle regulation and the possible pathway. We found that leptin stimulated VSMC proliferation and increased cell progression to S and G2/M phases. The expression of cyclinD1, phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and nuclear factor (NF)-kappaBp65 was increased. Treatment of the cells with leptin antagonist triple mutant attenuated the leptininduced ERK1/2 and NF-kappaB activation. These results suggested that leptin stimulated VSMC proliferation by promoting transition from G1 to S phase and ERK1/2 and NF-kappaB pathway might contribute to this procession.