Study for the pathogenesis of atherosclerosis.

由于来自不同领域的几项研究的合作工作，我们可以得到以下结果：1)我们在whhl -兔的动脉粥样硬化病变中证实了氧化LDL的存在（arterclerosis and Thrombosis, 1991）。2)我们已经证明氧化LDL可以增强巨噬细胞PGE2的产生和分泌。然而，在本项目中，我们发现巨噬细胞一旦被氧化LDL变成泡沫细胞，它们就不再能够产生PGE_2。我们发现，长期喂普罗布考（一种抗氧化剂）可以通过抑制氧化LDL的形成来阻止whhl兔动脉粥样硬化的形成。此外，普罗布考对WHHL家兔的动脉粥样硬化病变有明显的消退作用（Atherosclerosis, 1992）。4)普罗布考增强了巨噬细胞的趋化性。这可能解释普罗布考抗动脉粥样硬化的作用（动脉硬化和血栓1992）。5) Narumiya等人分离并克隆了前列腺素E受体的cDNA。化学。在出版社)。6) Dr. Yamada等人表明，人重组巨噬细胞集落刺激因子（M-CSF）在酶活性和mRNA水平的基础上增强了脂蛋白脂肪酶的产生和分泌。Yamada博士还通过DNA序列分析证明了5名不相关的日本家族性LPL缺乏症患者的基因异常（明显的点突变）（arterclerosis and Thrombosis 1991, JCI 1991）。Saito博士从培养的平滑肌细胞中展示了新的平滑肌细胞生长因子和迁移因子。现在他正在描述其特性（动脉粥样硬化1991，医学与生物学报1991）。8) Yamamoto博士在whhl兔的病变中发现了转移mRNA的表达，但在对照组中没有。他现在正在研究它的生物学意义（手稿准备）。9)我们证明，一旦HDL颗粒被氧化（氧化HDL），不再被氧化的HDL可以促进胆固醇从泡沫细胞流出（PNAS 1991）。Horiuchi博士从生物化学角度证明了巨噬细胞的内吞作用和随后的HDL分泌（BBA 1991）。少

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