Study on the significance of apo E in aherosclerosis

apo E在动脉粥样硬化中的意义研究

• 批准号: 05670407
• 负责人: ETO Masaaki
• 金额: $ 1.34万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670407/
• 关键词: apo E; lipoprotein; remnant; triglycevide; Cholesterol; Macrophage; apo E allele; atherogenicity; 動脈硬化; 脂質

Apolipoprotein E is one of the protein constituents of VLDL,VLDL remnants and chylomicron remnants, which are atherogenic lipoproteins. TG-rich lipoproteins and their remnants are taken up by macrophages and cause the accumulation of cholestervl ester (CE), and then the formation of foam cells. apo E plays an important role in the above process as a ligand for the lipoprotein receptors. The significance of Apo E in the pathogenesis of atheroscler osis was examined in this study. The frequencies of apo E2 and E4 were significantly higher in patients with ischemic heart disease than in controls. Apo E2 is associated with type III hyperlipoproteinemia (HLP) and hypertriglyceridemia (type IV HLP) , whereas apo E4 is associated with hyper-cholesterolemia (type IIa and IIb HLP). Thus, apo E2 and E4 are atherogenic. We established a method for apo E genotyping by PCR-RFLP.ApoE2 increased plasma RLP (remnant-like particles) and caused postprandial lipemia, which is thought to be atherogenic. RLP and TG-rich lipoproteins derived from NIDDM and apo E2-associated hyperlipemia enhanced the CE synthesis as compared with those derived fromcontrols. It is concluded that apo E plays an important role in atherosclerosis.

载脂蛋白E是VLDL、VLDL残余物和乳糜微粒残余物的蛋白质成分之一，它们是致动脉粥样硬化脂蛋白。富含TG的脂蛋白及其残余物被巨噬细胞摄取，引起胆固醇酯(CE)的积累，进而形成泡沫细胞。 apo E作为脂蛋白受体的配体在上述过程中发挥重要作用。本研究探讨了 Apo E 在动脉粥样硬化发病机制中的重要性。缺血性心脏病患者的apo E2 和E4 频率显着高于对照组。 Apo E2 与 III 型高脂蛋白血症 (HLP) 和高甘油三酯血症 (IV 型 HLP) 相关，而 apo E4 与高胆固醇血症 (IIa 和 IIb 型 HLP) 相关。因此，apo E2 和 E4 是致动脉粥样硬化的。我们建立了一种通过 PCR-RFLP 进行 apo E 基因分型的方法。ApoE2 增加血浆 RLP（残留样颗粒）并引起餐后脂血症，这被认为是致动脉粥样硬化的。与源自对照的脂蛋白相比，源自 NIDDM 和 apo E2 相关高脂血症的富含 RLP 和 TG 的脂蛋白增强了 CE 合成。结论apo E在动脉粥样硬化中起重要作用。

项目成果

Saito M,Eto M,Sato M,Makino M,Nunomura A,Chiba S,Miyagishi T,Naoe J.Miyamoto T,Ota K: "Apolipoprotein E4 and Alzheimer's disease" J Lipoprotein Res Soc. 13. 26-31 (1994)

Saito M、Eto M、Sato M、Makino M、Nunomura A、Chiba S、Miyagishi T、Naoe J.Miyamoto T、Ota K：“载脂蛋白 E4 和阿尔茨海默病”J 脂蛋白研究学会。

衛藤雅昭: "糖尿病患者由来TG-richリポ蛋白のatherogenicity" 糖尿病大血管障害. 2. 115-120 (1993)

Masaaki Eto：“源自糖尿病患者的富含 TG 的脂蛋白的致动脉粥样硬化性”糖尿病大血管病。 2. 115-120 (1993)

Eto M,Chiba H,Saito M,Nomura M,Okada M,Miyamoto Y,Abiko A,Matsumoto S,Morikawa A,Iwashima Y,Makino I: "Plasma apo E-rich HDL and apo E genetic polymorphism in normolipidemic subjects." J Lipoprotein Res Soc. 13. 19-23 (1994)

Eto M、Chiba H、Saito M、Nomura M、Okada M、Miyamoto Y、Abiko A、Matsumoto S、Morikawa A、Iwashima Y、Makino I：“正常血脂受试者中血浆载脂蛋白 E 丰富的 HDL 和载脂蛋白 E 遗传多态性。”

Saito M, Eto M: "Apo lipoprotei E4 and Alyheimeis disease" J. Lipoprotei Pes Soc. 13. 26-31 (1994)

Saito M、Eto M：“Apo lipoprotei E4 和 Alyheimeis 病”J. Lipoprotei Pes Soc。

H.Chiba: "Increased plasma apolipoprotein E-rich high-density lipoprotein and its effect on serum high-density lipopro tein...." Biochemical Medicine and Metabolic Biology. 49. 79-89 (1993)

H.Chiba：“血浆载脂蛋白 E 丰富的高密度脂蛋白增加及其对血清高密度脂蛋白的影响......”生化医学和代谢生物学。