Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2074-2081
© 1997 American Heart Association, Inc.
Articles |
Homocysteine as a Risk Factor for Vascular Disease
Enhanced Collagen Production and Accumulation by Smooth Muscle Cells
From the Department of Cell Biology, Research Institute, Cleveland Clinic Foundation, Ohio. Drs Majors and Pezacka are now affiliated with the Department of Human Genetics, Allegheny University of the Health Sciences, Pittsburgh, Pa.
Abstract An increased plasma homocysteine level is an independent risk factor for vascular disease. However, the pathological mechanisms by which homocysteine promotes atherosclerosis are not yet clearly defined. Arterial smooth muscle cells cultured in the presence of homocysteine grew to a higher density and produced and accumulated collagen at levels significantly above control values. Homocysteine concentrations as low as 50 µmol/L significantly increased both cell density and collagen production. Cell density increased by as much as 43% in homocysteine-treated cultures. Homocysteine increased collagen production in a dose-dependent manner. Smooth muscle cells treated with homocysteine at concentrations 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-treated cultures. Addition of aquacobalamin to homocysteine-treated cultures controlled the increase in smooth muscle cell proliferation and collagen production. These results indicate a cellular mechanism for the atherogenicity of homocysteine and provide insight into a potential preventive treatment.
Key Words: collagen • atherosclerosis • homocysteine • smooth muscle cell • extracellular matrix
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