Modulation of collagen synthesis by tumor necrosis factor alpha in cultured vascular smooth muscle cells

Collagen synthesis in vascular smooth muscle cells (SMCs) after exposure to tumor necrosis factor alpha (TNF-α) was investigated using a culture system. The synthesis of collagenase-digestible proteins (CDP) and noncollagenous proteins (NCP) was evaluated by the [³H]proline incorporation. It was shown that TNF-α markedly suppresses the incorporation of [³H]proline into both CDP and NCP in confluent cultures of SMCs but not in sparse cultures of the cells. Such a marked suppression by TNF-α was not observed in confluent bovine aortic endothelial cells and human fibroblastic IMR-90 cells. In confluent SMCs, the synthesis of CDP was more strongly inhibited by TNF-α than that of NCP. When the CDP synthesis was stimulated by transforming growth factor beta, TNF-α suppressed the stimulation in both confluent and sparse SMCs. Human SMCs synthesized types I, III, IV and V collagens; TNF-α markedly decreased the relative proportion of types IV and V. It was therefore suggested that TNF-α modulates the collagen synthesis by SMCs depending on their cell density and modifies the formation of atherosclerotic lesions.