Vascular Smooth Muscle Cells In Culture Express Tumor Necrosis Factor-Alpha That Suppresses Collagen Synthesis Depending On Cell Density

Tumor necrosis factor-a (TNF-alpha) has been implicated in the pathogenesis of atherosclerosis through influence on vascular smooth muscle cell behavior. However, little is known about the expression and function of endogenous TNF-alpha in the cells. Dense and sparse cultures of bovine aortic smooth muscle cells were prepared and the expression of TNF-alpha and regulation of collagen synthesis by endogenous TNF-alpha were investigated. The results indicate that dense and sparse vascular smooth muscle cells express endogenous TNF-alpha that suppresses the synthesis of collagen (types I and III) only when the cell density is high; suppression was also observed in human and rabbit aortic smooth muscle cells. Transforming growth factor-beta-stimulated collagen synthesis in bovine aortic smooth muscle cells and the stimulation was significantly suppressed by endogenous TNF-alpha when cell density was high. The present data suggest that vascular smooth muscle cells express endogenous TNF-alpha that is involved in the suppressive regulation of collagen synthesis depending on the cell density.