[Peroxidation injury of endothelial cells and atherosclerosis development]

Lipid peroxidation was initiated and then facilitated in the cultured aorta and a defined segment of rabbit carotid artery with thiol-oxidizing agent, diamide. The effects of lipid peroxidation on endothelial cells consisted of damage to the biomembranes and subcellular organelles and inhibition of PGI2 synthesis. Diamide (5 x 10(-3) mol/L) was introduced into a defined segment of carotid artery and perfusion was taken on at various intervals, i.e. for 2 hs, 12 hs, 1 day, 2 days, 3 days, 7 days, and 14 days. Examinations showed injury of the endothelial cells, but neither cell denudation and exposure of the subendothelium was obtained. One day after the injury, a large number of monocytes were seen attaching to the intact endothelium with cell immigration toward the intima. Two weeks later, intimal thickening was obtained. In rabbits fed with cholesterol diet beforehand for 8-10 weeks, this was combined with endothelial cell injuries. There was also atherosclerotic lesions in intima involving proliferation of the smooth muscle cells in the carotid arteries. These results suggested that endothelial cell injury induced by lipid peroxide might play an important role in atherogenesis.