Ascorbate Affects Proliferation of Guinea-pig Vascular Smooth Muscle Cells by Direct and Extracellular Matrix-mediated Effects |
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Authors: | Vadim O Ivanov Svetlana V Ivanova Aleksandra Niedzwiecki |
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Institution: | Linus Pauling Institute of Science, 440 Page Mill Road, Palo Alto, 94306, CA, USA |
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Abstract: | Proliferation of smooth muscle cells and deposition of extracellular matrix proteins are important events in the formation of atherosclerotic plaques. We have investigated the direct and matrix-mediated effects of ascorbate on the proliferation rate of vascular smooth muscle cells (VSMC) isolated from the guinea-pig aorta. In the presence of ascorbate, cells showed a bi-phasic growth pattern. At 125μmascorbate, 3H]-thymidine incorporation was stimulated 25%. However, higher concentrations of ascorbate gradually decreased cell-incorporated radioactivity up to 50% at 2 mmascorbate. These effects of ascorbate on DNA synthesis in VSMC were paralleled by the changes in cell number and were not due to ascorbate cytotoxicity. Alpha-tocopherol (0.1 mm), individually and in combinations with 1 mmascorbate, also inhibited DNA synthesis in VSMC. Ascorbate also influenced proliferation of smooth muscle cells through matrix-mediated effect. New VSMC culture plated on extracellular matrices deposited by smooth muscle cells in the presence of 0.1–1 mmascorbate had up to 50% lower proliferation rate than on matrices from ascorbate-deficient cells, as assessed by 3H]-thymidine incorporation. This effect was independent from alpha-tocopherol and specific inhibitors of collagen synthesis:l-azetidine-2-carboxylic acid and pyridine-2,4-dicarboxylic acid. An ascorbate-dependent matrix effect was specific for smooth muscle cells grown on VSMC and human skin fibroblast-originated matrices, but not for human vascular endothelial cells. The possible involvement of ascorbate in the regulation of smooth muscle cells proliferation by its antioxidant/pro-oxidant effects and regulation of extracellular matrix composition are discussed. |
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Keywords: | Smooth muscle cell Extracellular matrix Proliferation Ascorbic acid Antioxidant Collagen |
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