Vascular Smooth Muscle Cells in Culture Express Tumor Necrosis Factor-α That Suppresses Collagen Synthesis Depending on Cell Density

Abstract

Tumor necrosis factor-α (TNF-α) 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-α in the cells. Dense and sparse cultures of bovine aortic smooth muscle cells were prepared and the expression of TNF-α and regulation of collagen synthesis by endogenous TNF-α were investigated. The results indicate that dense and sparse vascular smooth muscle cells express endogenous TNF-α 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-β stimulated collagen synthesis in bovine aortic smooth muscle cells and the stimulation was significantly suppressed by endogenous TNF-α when cell density was high. The present data suggest that vascular smooth muscle cells express endogenous TNF-α that is involved in the suppressive regulation of collagen synthesis depending on the cell density.