[Studies on atherosclerosis with an animal model].
Atherosclerosis is a fundamental cause of life-threatening disorders, such as ischemic heart disease or stroke. Therefore, prevention and treatment of atherosclerosis is a matter of importance. In atherosclerotic lesions, there are many foam cells which contain large amounts of cholesteryl ester. In particular, most of these foam cells in the early stage of atherosclerosis derive from monocytes/macrophages. Today, foam cell transformation of macrophages in subendothelial space is considered to occur by a mechanism in which macrophages take up oxidized low density lipoprotein. We have already discovered that atherosclerosis of Watanabe heritable hyperlipidemic rabbits, an animal model for hereditary hyperlipidemia and severe atherosclerosis, could be prevented by probucol. This drug was originally developed as an antioxidant, and the mechanism of prevention of atherogenesis with this drug is considered that it prevents oxidative modification of LDL. On the other hand, probucol also causes regression of xanthoma in patients with familial hypercholesterolemia. This effect implies that probucol can be effective for treatment of atheromatous lesions, because xanthoma is a lesion which consists of macrophage-derived foam cells. However, the precise mechanism of probucol in causing regression of xanthoma has not been clarified. Considering these observations, we paid special attention to the oxidative modification of high density lipoprotein (HDL). HDL makes contact with foam cells in subendothelial space and stimulates efflux of cholesterol. This is the very place where oxidative modification of LDL is considered to occur. Therefore, it is rational to attempt to determine what would happen when HDL is oxidized and whether probucol could prevent oxidative modification of HDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Nagano
Y
Y
Department of Geriatric Medicine, Faculty of Medicine, Kyoto University.
Kita
T
T
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control / Q000628:therapy; D004195:Disease Models, Animal; D011817:Rabbits