HOMOCYSTEINE AS A RISK FACTOR FOR VASCULAR-DISEASE - ENHANCED COLLAGEN PRODUCTION AND ACCUMULATION BY SMOOTH-MUSCLE CELLS

An increased plasma homocysteine level is an independent risk factor f or vascular disease. However, the pathological mechanisms by which hom ocysteine promotes atherosclerosis are not yet clearly defined. Arteri al smooth muscle cells cultured in the presence of homocysteine grew t o a higher density and produced and accumulated collagen at levels sig nificantly above control values. Homocysteine concentrations as low as 50 mu mol/L significantly increased both cell density and collagen pr oduction. Cell density increased by as much as 43% in homocysteine-tre ated cultures. Homocysteine increased collagen production in a dose-de pendent manner. Smooth muscle cells treated with homocysteine at conce ntrations observed in patients with hyperhomocysteinemia had collagen synthesis rates as high as 214% of control values. Likewise, collagen accumulation in the cell layer was nearly doubled in homocysteine-trea ted cultures. Addition of aquacobalamin to homocysteine-treated cultur es controlled the increase in smooth muscle cell proliferation and col lagen production. These results indicate a cellular mechanism for the atherogenicity of homocysteine and provide insight into a potential pr eventive treatment.