EXPERIMENTAL STUDY ON ATHEROSCLEROSIS –AN ATTEMPT AT ITS PREVENTION AND TREATMENT

Electron microscopical analysis of endothelial linings of the aortic lumen and of the vasa vasorum was made in man, rhesus monkey, dog, rabbit, rat, chicken and pigeon with reference to permeability of the arterial wall, because cholesterol and other substances accumulating in atheromatous lesions have been known to be transported mainly by infiltration into the lesions from the blood stream across the endothelial lining. Porous capillaries were found in vasa vasorum of man, rabbit and pigeon and a well developed vacuole system in the endothelial cells of man and chicken. For the present experiment of atherosclerosis the rabbit has been chosen. In the succeeding experiments we found substances capable of inhibiting the edematous arterial reaction such as pyridinolcarbamate and its derivatives as well as estrogens and glucocorticoids. We have tested these substances for the prevention of atherosclerosis of cholesterol‐fed rabbits and also for the treatment of established atherosclerosis of the animals. The first important finding was the correlation between their inhibiting potency against the edematous arterial reaction and their property of preventing atherosclerosis. The second Important finding was appearance of atrophy, necrosis and calcification of arterial wall along with the atheroma‐preventive effect of estrogen and prednisolone and the absence of such effects in pyridinolcarbamate, while the latter substance enhances the regeneration of smooth muscles in the lesions. Dosages of 10 to 30 mg per kg of pyridinolcarbamate given by mouth daily have shown the atheromatous mass with foam cells, necrosis and degenerative foci being replaced by regenerated smooth‐muscle, collagen and elastic fibers, and the cholesterol content of arterial wall was definitely reduced in the course of 6 to 30 weeks of the treatment, without any untoward effect. Histoenzymatic analysis revealed the increased enzymatic activity of glycolytic enzymes Including glucose‐6‐phosphate dehydrogenase in the arterial wall of animals treated with pyridinolcarbamate and the decreased enzymatic activity of glycolytic enzymes in that of animals treated by estrogen. The results reported in this paper show that the author's edematous arterial reaction has opened a way toward finding antiatherosclerotic agents which may prove to be useful in the prevention and treatment of human atherosclerosis. ACTA PATH. JAP. 19: 15˜43, 1969.