AimTo explore the possibility of homocysteine-induced vascular smooth muscle cell (VSMC) proliferation via N-methy-D-aspartate (NMDA) receptor and its possible terminal target molecules.MethodsVSMC proliferation was induced by homocysteine, and the VSMC was treated with NMDA receptor antagonist MK801.The rate of proliferation of VSMC were detected by the way of MTT.Cell cycle distribution were determined by flow cytometer.The cyclin D1 mRNA expression in cultured VSMC were measured by RT-PCR.ResultsHomocysteine significantly stimulated VSMC proliferation, promoted VSMC convert from the G0/G1 to S phase, and increased cyclin D₁ mRNA expression. MK801, however, inhibited the proliferation of VSMC by homocysteine, the conversion from G0/G1 to S phase and the expression of cyclin D₁ mRNA were synchronously inhibited.All these effects showed significant dose-dependent manner.ConclusionThe proliferation-promoting effect of homocysteine on VSMC might be partly mediated by NMDA receptor and ultimately achieved through the cyclin D pathway.