TNF-α–Induced Migration of Vascular Smooth Muscle Cells Is MAPK Dependent

Abstract

—Migration of vascular smooth muscle cells (VSMC) is a key event in neointimal formation and atherosclerosis that may be linked to the accumulation of inflammatory cells and release of chemotactic cytokines. Tumor necrosis factor-α (TNF-α) induces chemotaxis of inflammatory cells and fibroblasts, but little is known about chemotactic signaling by TNF-α in VSMC. The aim of this study was to investigate the role of TNF-α in VSMC migration and to elucidate the chemotactic signaling pathways mediating this action. TNF-α (50 to 400 U/mL) induced migration of cultured rat aortic VSMC in a dose-dependent manner. Because activation of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK) is known to be required in platelet-derived growth factor–directed and angiotensin II–directed migration of these cells, we used the MAPK-inhibitor PD98059 to determine if chemotactic signaling by TNF-α involves the MAPK pathway as well. We found that TNF-α–directed migration was substantia...