Tumor Necrosis Factor-α Activates Smooth Muscle Cell Migration in Culture and Is Expressed in the Balloon-Injured Rat Aorta

Abstract

In experimental models of atherosclerosis, activation of smooth muscle cell (SMC) migration from the media to the intima is preceded by intimal accumulation of inflammatory cells, suggesting that cytokines may be involved in this process. The present study demonstrates that tumor necrosis factor-α (TNF-α) regulates cytoskeletal organization of SMCs by inducing depolymerization of actin stress fibers and dispersion of vinculin from sites of focal adhesion and stimulates the migration of cultured human SMCs in a dose-dependent manner. Moreover, TNF-α induces rapid activation of the c-ets-1 gene, which codes a transcription factor known to regulate enzymes important for matrix degradation during cell migration. Balloon catheter injury of the rat femoral artery resulted in medial expression of TNF-α within 6 hours. This expression appeared to be localized to SMCs and remained elevated until SMCs began to migrate into the intima 7 days after injury. These findings demonstrate that TNF-α has a stimulatory effect on SMC migration and suggest that TNF-α may be involved in the intimal recruitment of SMCs during plaque formation.