Study for the pathogenesis of atherosclerosis.

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As a result of collaborating work among several researches from different fields, we could get following results ;1) We demonstrated the existence of oxidized LDL in the lesion of atherosclerosis from WHHL-rabbits (Arteriosclerosis and Thrombosis 1991).2) We have already showed that oxidized LDL enhances the production and secretion of PGE2 from macrophages. However in this project, we found that once macrophages become foam cells by oxidized LDL, no longer they could produce PGE_2. (submit)3) We discovered that long term feeding of probucol, an antioxidant, could prevent the progression of atheromatous formation in WHHL-rabbits as a result of inhibition of oxidized LDL formation. In addition, probucol could regress the atheromatous lesionsin WHHL rabbits (Atherosclerosis 1992).4) We showed that probucol enhanced the chemotaxis of macrophages. It might explain the probucol antiatherogenic effects (Arteriosclerosis and Thrombosis 1992).5) Dr. Narumiya et al. isolated and cloned a cDNA f … More or prostaglandin E receptor (J. Biol. Chem. in press).6) Dr. Yamada et al. showed that human recombinant macrophage-colony stimulating factor (M-CSF) enhanced lipoprotein lipase production and secretion on the basis of both enzyme activity and mRNA level. Dr. Yamada also demonstrated the gene abnormality (distinct point mutations) of five unrelated Japanese patients with familial LPL deficiency by DNA sequence analysis (Arteriosclerosis and Thrombosis 1991, JCI 1991).7) Dr. Saito demonstrated the new smooth muscle cell growth factor and migration factor from cultured smooth muscle cells. Now he is characterizing its property (Atherosclerosis 1991, Acta Medica et Biologica 1991).8) Dr. Yamamoto found the expression of transfering mRNA in WHHL-rabbit's lesions, but not in control rabbits. He is now studying its biological meaning (manuscript preparation).9) We demonstrated once HDL particles are oxidized (oxidized HDL), no longer oxidized HDL could promote the cholesterol efflux from foam cells (PNAS 1991). Dr. Horiuchi demonstrated biochemically that the endocytosis and subsequent resecretion of HDL in macrophages (BBA 1991). Less