HYPERREACTIVE ARTERIAL ENDOTHELIAL CELLS: A CLUE FOR THE TREATMENT OF ATHEROSCLEROSIS

Abstract

Arterial endothelial cells, which are capable of phagocytizing carbon particles of the same size as beta- and pre-beta-lipoprotein, were found only in endothelial cells of arterial segments susceptible to atheromatous changes in susceptible animal species, and the distribution closely corresponded to the susceptibility. The distribution of such endothelial cells is dense in large arteries, in the openings to their branches, especially in downstream portions, of rabbits, hens, and cocks; however, the distribution is relatively scanty in arteries of rhesus monkeys and is very scanty in dogs. Carbon particles were also rare in the suckling rabbit and tended to increase with age. They were not found in Wistar rats but were found in spontaneously hypertensive rats, which showed a characteristically diffuse distribution, even in relatively small arteries. The carbon particles, phagocytized, were released to the subendothelial space but were difficult to pass through the internal elastic lamina and tended to stagnate there for more than one month. The authors therefore call these cells hyperreactive endothelial cells. Various vasoactive substances, such as angiotensin II, histamine, and serotonin, significantly enhanced the phagocytic activities of arotic endothelial cells in rabbits; epinephrine and norepinephrine also slightly enhanced these activities. Various smooth muscle relaxants, such as ATP, pyridinol carbamate (ATP synthesis-enhancing substance), cycli-AMP, dibutyryl cycli-AMP, phthalazinol (cyclic-AMP phosphodiesterase inhibitor), iproveratril (calcium entry-inhibiting substance), colchicine, and vinblastine, with their different modes of action, commonly inhibited phagocytic activities, a finding that suggests a significant role for contractile protein in the permeability problem of atherogenesis. The atheromatous lesions of cholesterol-fed rabbits exhibited a striking increase in hyperreactive endothelial cells, accompanied by a marked rise in the activity of low-Km cyclic-AMP phosphodiesterase activity in atheromatous lesions and adjacent muscular layers, especially in rabbits with rapidly progressing atheroma.