INHIBITION OF VASCULAR SMOOTH-MUSCLE CELL-MIGRATION BY INTACT ENDOTHELIUM IS NITRIC OXIDE-MEDIATED - INTERFERENCE BY OXIDIZED LOW-DENSITY LIPOPROTEINS

Migration of vascular smooth muscle cells (SMCs) leading to neointimal hyperplasia is an early and cardinal feature of atherogenesis. Migrat ion of rat aortic SMCs from an upper chamber towards a lower one has b een studied in a microchemotaxis (Boyden) chamber. Spontaneous migrati on of SMCs was practically prevented by the presence of endothelium in the lower chamber and was reduced if endothelial cells were substitut ed with endothelial cell-conditioned medium. Endothelial cells which h ad been treated with either the inhibitor of protein synthesis cyclohe ximide or nitric oxide synthesis N-G-nitro-1-arginine showed no inhibi tory effect on SMC migration. Addition of a nitric oxide donor S-nitro so-N-acetylpenicillamine to cell-free medium in the lower chamber prev ented SMC migration. Addition of native LDL to endothelial cells had n o effect on SMC migration, while (UV light) oxidised LDL completely ab olished the inhibitory effect of endothelial cells on SMC migration. I t is concluded that via nitric oxide, endothelium exerts a powerful in hibitory effect on SMC migration. This effect of intact endothelium is completely abolished by oxidised LDL applied in a concentration, whic h is relevant to those measured in plasma of patients with severe coro nary artery disease. It is suggested that oxidised LDL may contribute to the pathogenesis of atherogenesis by stimulating migration of SMCs from media to the intima via abolishing the physiological inhibitory e ffect of normal endothelium.