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 homocysteine-mediated alterations in the thromboregulatory properties of endothelial cells, comparatively little is known about homocysteine-modulated smooth muscle cell function. We observed that exposure of human aortic smooth muscle cells to pathophysiologically relevant concentrations of homocysteine results in concentration-dependent increases in cytokine-induced MCP-1 and IL-8 secretion. RNase protection assays revealed that both MCP-1 and IL-8 mRNA concentrations are increased in homocysteine-treated smooth muscle cells when compared to cells activated with cytokines alone. Homocysteine treatment also increased cytosolic-to-nuclear translocation of the p65 and p50 subunits of the Rel/NF-κB family of transcription factors but had no effect on AP-1 activation. Cumulatively, these data suggest that homocysteine may increase monocyte recruitment into developing atherosclerotic lesions by upregulating MCP-1 and IL-8 expression in vascular smooth muscle cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44529/1/10753_2004_Article_297162.pd