The effect of homocysteine on DNA synthesis in cultured human vascular smooth muscle

Elevated plasma homocysteine is an established risk factor for vascular disease although the mechanisms are unclear. Homocysteine has been reported to stimulate DNA synthesis and proliferation in rat aortic smooth muscle cells. Human vascular smooth muscle cells (HVSMC) from saphenous veins (n = 8), internal mammary arteries (n = 6) and umbilical arteries (n = 2) were studied. To reflect DNA synthesis, H-3-thymidine incorporation, during 24 h exposure to homocysteine in concentrations from 0.0625 to 10 mM, was studied. Incorporation was significantly increased up to 0.5 or 1 mM and thence was progressively depressed, the maximum stimulation being 24 +/- 5(S.E.)% in vein (P < 0.005) and 34 +/- 4% in mammary artery (P < 0.001) while incorporation fell to approximately 25% of the control values at 10 mM (P < 0.001). Qualitatively similar results were obtained in umbilical arteries. Homocysteine had a biphasic effect on DNA synthesis in cultured HVSMC but the higher inhibitory concentrations are well above those commonly found in vivo. While the conditions of exposure to homocysteine render close analogy to the clinical situation impossible, homocysteine can stimulate HVSMC, offering one possible mechanism for the involvement of homocysteine in the pathogenesis of atherosclerosis. (C) 1998 Elsevier Science Ireland Ltd.