Matrix, matrix metalloproteinases and smooth muscle cell function in atherosclerosis

摘要

Collagens in the extracellular matrix play important roles modulating the vascular response to injury during the progression of atherosclerosis.and restenosis. Collagen can regulate smooth muscle cell (SMC) proliferation, and SMC and macrophage migration and proteinase production. The discoidin domain receptors, DDR1 and DDR2, are novel transmembiane collagen receptors with tyrosine kinase activity, and signal to upregulate matrix metalloproteinase (MMP) expression Research in our laboratory has been focused on the expression and functions of DDR 1 in the cardiovascular system DDR1 expression is increased following vascular injury.We have shown that DDR1 - / -^sSMCs have a reduced capacity to proliferate and migrate, and have reduced MMP expression compared with DDR1+/+ cells.We injured the carotid arteries of DDR1 - / - mice and found a dramatic reduction in neointimal thickening.These studies suggest that DDR1 plays a role in arterial wound repair and helps to elucidate the roles of collagen and the DDRs in atherosclerosis and restenosis.