Correlation of Lipoprotein Abnormalities in Childhood withe the Risk for Atherosclerotic Coronary Heart Disease (CAD) in Adulthood (Is abnormaltites in childhood a risk factor for CAD? )

儿童期脂蛋白异常与成年期动脉粥样硬化性冠心病 (CAD) 风险的相关性（儿童期异常是 CAD 的危险因素吗？）

• 批准号: 06670809
• 负责人: OHTA Takao
• 金额: $ 1.41万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670809/
• 关键词: LpA-I; A-II; Atherosclerosis; FERHDL; LDL size; Small LDL; small LDL; LDL size; LpA-1; A-II

1.We investigated the effects of subclasses of LpA-I [high density lipoprotein (HDL) containing only apoA-I] on cholesterol esterification in plasma and net cholestrol efflux from foam cells. LpA-I was composed of particles of three different sizes : large (Lg-LpA-I), medium (Md-LpA-I) and small (Sm-LpA-I). Plasma concentrations of LpA-I were positively correlated only with the level of Lg-LpA-I.Plasma concentrations of Lg-LpA-I were inversely correlated with the rate of cholesterol esterification in plasma and VLDL and LDL-depleted plasma (FERplasma and FER_<HDL>). When macrophage foam cells were incubated with Md-and Sm-LpA-I,cellular cholesterol mass was reduced by approximately 70%. In contrast, the cellular cholesterol-reducing capacity of Lg-LpA-I was negligible. Lg-LpA-I inhibited net cholesterol removal from foam cells that was mediated by Md-and Sm-LpA-I and cholesteryl ester production with these particles. These results suggest that Md-and Sm-LpA-I may actively participate i … More n cellular cholesterol removal and cholesterol esterification in plasma and HDL,while Lg-LpA-I may regulate these functions of Md-and Sm-LpA-I.2.We examined the correlations between low-density-lipoprotein (LDL) particle size and both FER_<HDL> and plasma lipid levels. FER_<HDL> and plasma triglyceride were negatively, and HDL-cholesterol was positively, correlated with LDL particle size (r=-0.728, -0.598and0.572, p>0.0001). Stepwise multiple regression analysis revealed that FER_<HDL> was most significantly associated with LDL particle size. Since FER_<HDL> is regulated by the plasma consentration of LpA-I (HDL containig apoA-I but not apoA-II), which is the anti-atherogenic fraction of HDL,the present results suggest that the regulation of LDL particle size may be part of the anti-atherogenic nature of LpA-1.3.Qualitative and quantitative changes of LpA-I in children with low plasma LpA-I were indistinguishable from those in patients with coronary artery disease (CAD) with low plasma LpA-I.All of our data suggest that children with low plasma LpA-I are high risk for CAD. Less

1.我们研究了脂蛋白A-Ⅰ（仅含载脂蛋白A-Ⅰ的高密度脂蛋白（HDL））亚类对血浆胆固醇酯化和泡沫细胞胆固醇净流出的影响。LpA-I由三种不同尺寸的颗粒组成：大（Lg-LpA-I）、中（Md-LpA-I）和小（Sm-LpA-I）。血浆LpA-I浓度仅与Lg-LpA-I水平呈正相关。血浆Lg-LpA-I浓度与血浆及VLDL和LDL耗竭血浆中胆固醇酯化率（FERplasma和FER_1）呈负相关<HDL>。当巨噬泡沫细胞与Md-和Sm-LpA-I孵育时，细胞胆固醇质量减少约70%。相反，Lg-LpA-I的细胞胆固醇降低能力可以忽略不计。Lg-LpA-I抑制泡沫细胞的净胆固醇清除，这是由Md-和Sm-LpA-I介导的，并与这些颗粒的胆固醇酯的产生。这些结果表明，Md-和Sm-LpA-I可能积极参与了 ...更多信息 Lg-LpA-I可能调节Md-1和Sm-LpA-I的上述功能。2.我们研究了低密度脂蛋白（LDL）颗粒大小与FER_2<HDL>和血脂水平的关系。血浆<HDL>胆固醇与LDL颗粒大小呈负相关（r=-0.728、-0.598和0.572，P&gt;0.0001）。多元逐步回归分析显示，FER_<HDL>与LDL颗粒大小的相关性最显著。由于FER_1<HDL>受血浆LpA-I浓度的调节，（HDL含有apoA-I但不含apoA-II），其是HDL的抗动脉粥样硬化组分，结果提示，LDL颗粒大小的调节可能是LpA-1抗动脉粥样硬化性质的一部分。3.低血浆LpA-I儿童与冠心病（CAD）患者LpA-I的定性和定量变化无明显区别。低血浆LpA-I的儿童是冠心病的高危人群。少

项目成果

Ikeda Yoichiro: "Interaction between apoA-I-containing lipoproteins and lecithin: cholesterol acyltransferase." Biochim Biophys Acta. 1215. 307-313 (1994)

池田洋一郎：“含 apoA-I 的脂蛋白与卵磷脂之间的相互作用：胆固醇酰基转移酶。”

Ohta Takao: "Structural and functional differences of subspecies of apoA-I-containing lipoproteins in patients with plasma cholesteryl ester transfer protein deficiency." J Lipid Res. 36. 696-704 (1995)

Ohta Takao：“血浆胆固醇酯转移蛋白缺乏症患者中含 apoA-I 的脂蛋白亚种的结构和功能差异。”

Takata Kouki: "A new case of apoA-I deficiency showing codon 8 nonsense mutation of the apoA-I gene without evidence of coronary heart disease." Arterioscler Thromb Vasc Biol. 15. 1866-1874 (1995)

Takata Kouki：“一例新的 apoA-I 缺陷病例显示 apoA-I 基因密码子 8 无义突变，但没有冠心病的证据。”

Suginohara Yoshiko: "The heparin-bound fraction of human lipoprotein-deficient serum inhibits endocytic uptake of oxidized low density lipoprotein by macrophages." Atherosclerosis. 120. 167-179 (1996)

Suginohara Yoshiko：“人脂蛋白缺乏血清中的肝素结合部分抑制巨噬细胞对氧化低密度脂蛋白的内吞摄取。”

Kajikawa Mikio: "Lactoferrin inhibits cholesterol accumulation in macrophages mediated by acetylated or oxidized low density lipoproteins" Biochim Biophys Acta. 1213. 82-90 (1994)

Kajikawa Mikio：“乳铁蛋白抑制乙酰化或氧化低密度脂蛋白介导的巨噬细胞中胆固醇积累”Biochim Biophys Acta。