Studies on the Preventive System Against Atherosclerosis Based on the Discovery of Cases With Choles-Terol Ester Transfer Protein Deficiency.

基于发现胆固醇-三醇酯转移蛋白缺陷病例的动脉粥样硬化预防系统研究。

• 批准号: 01480289
• 负责人: MATSUZAWA Yuji
• 金额: $ 4.29万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480289/
• 关键词: Cholestaryl ester travster protein; Reverse cholesterol transport; Hyper HDL cholesherolemia; Atherosc lerosis; High density lipoprotein; Low density lipoprotein; CETP gene; コレステロ-ルエステル転送蛋白; HDL; LDL; 動脈硬化防御機構; 肝性リパ-ゼ; 角膜混濁; LDL-レセプタ-

High density lipoprotein has been believed to play an important role in protecting atherosclerosis and the deficiency of HDL causes premature atherosclerosis. However, we have reported some types of hyper HDL cholesterolemia may be accompanied with lipid storage including coronary atherosclerosis and corneal opacities similar to HDL deficiency. In this study, we found the cases with hyper HDL cholesterolemia with Chdesterol Ester Transfer Protein (CETP) deficiency and studied the lipoprotein metabolism in this metabolic disorder to clarify physiological roles of CETP in the preventive system against atherosclerosis. HDL pasticles were shown to be markidly enlarged with high content of cholesteryl ester (CE) and apolipoprotein E. We demonstrated that LDL penticles also became abnormal in CETP deficiency. Namely, particles became polydisperse and consist of two groups different in size. These result suggests that CETP may play an important role in transferring CE from HDL to LDL and forming mature and homogeneous LDL.The defect of this process may result in cholesterol transport system from peripheral tissues to liver and finally cause the impairment of prevention against lipid storage in tissues.

高密度脂蛋白被认为在保护动脉粥样硬化中起重要作用，缺乏高密度脂蛋白可导致过早动脉粥样硬化。然而，我们已经报道了一些类型的高HDL胆固醇血症可能伴随着脂质储存，包括冠状动脉粥样硬化和角膜混浊，类似于HDL缺乏。本研究通过对高HDL胆固醇血症合并CETP缺乏的病例进行研究，阐明CETP在动脉粥样硬化预防系统中的生理作用。高密度脂蛋白颗粒明显增大，胆固醇酯（CE）和载脂蛋白e含量高。我们发现，在CETP缺乏时，低密度脂蛋白颗粒也变得异常。也就是说，粒子变得多分散，由两组大小不同的粒子组成。这些结果提示CETP可能在CE从HDL向LDL转化并形成成熟、均匀的LDL过程中起重要作用。这一过程的缺陷可能导致胆固醇从外周组织转运到肝脏，最终导致组织脂质储存的预防功能受损。

项目成果

S.Yamashita,Y.Matsuzawa et al.: "Total deficiency of plasma cholesteryl ester transfer protein in subjects homozygous and heterozygous for the intron 14 splicing defect." Biochem Biophys Res.Commun. 170. 1346-1351 (1990)

S.Yamashita、Y.Matsuzawa 等人：“纯合子和杂合子受试者的血浆胆固醇酯转移蛋白完全缺乏内含子 14 剪接缺陷。”

松沢 佑次他: "HDL代謝におけるアポ蛋白と細胞のinteractionおよびその異常" 動脈硬化. 18. 253-261 (1990)

Yuji Matsuzawa 等人：“脱辅基蛋白-细胞相互作用及其在 HDL 代谢中的异常”动脉硬化。

N. Sakai, Y. Matsuzawa, K. Hirano, et al.: "Detections of two species of low density lipoprotein particles in cholesteryl ester transfer protein deficiency." Arteriosclerosis and Thrombosis. 11. 71 (1991)

N. Sakai、Y. Matsuzawa、K. Hirano 等人：“检测胆固醇酯转移蛋白缺陷中的两种低密度脂蛋白颗粒。”

酒井 尚彦,松沢 佑次他: "内科MOOK No40 動脈硬化の防禦機構" 垂井清一郎編(金原出版), 9 (1990)

Naohiko Sakai、Yuji Matsuzawa等：《内科MOOK第40号：动脉硬化的预防机制》，樽井精一郎编辑（金原出版社），9（1990年）

Y.Matsuzawa et al.: "Selective reduction of choledesterol in HDL_2 fraction by piopucal in familial hyper cholesterolemia and hyperHDL2 cholesterdemia with abnormal cholesteryl ester transter" Am. J. Cardial.62. 66B-72B (1988)

Y.Matsuzawa 等人：“在家族性高胆固醇血症和伴有异常胆固醇酯转运的高 HDL2 胆固醇血症中，通过 piopucal 选择性降低 HDL_2 部分中的胆固醇”Am。