Homocysteine augments cytokine-induced chemokine expression in human vascular smooth muscle cells: Implications for atherogenesis

Hyperhomocysteinemia is an independent risk factor for atherosclerosis and atherothrombosis. While in vitro studies have revealed a number of homocyst eine-mediated alterations in the thromboregulatory properties of endothelia l cells, comparatively little is known about homocysteine-modulated smooth muscle cell function. We observed that exposure of human aortic smooth musc le cells to pathophysiologically relevant concentrations of homocysteine re sults in concentration-dependent increases in cytokine-induced MCP-1 and IL -8 secretion. RNase protection assays revealed that both MCP-1 and IL-8 mRN A concentrations are increased in homocysteine-treated smooth muscle cells when compared to cells activated with cytokines alone. Homocysteine treatme nt also increased cytosolic-to-nuclear translocation of the p65 and p50 sub units of the Rel/NF-kappaB family of transcription factors but had no effec t on AP-1 activation. Cumulatively, these data suggest that homocysteine ma y increase monocyte recruitment into developing atherosclerotic lesions by upregulating MCP-1 and IL-8 expression in vascular smooth muscle cells.