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动脉壁中的阿波利波蛋白A1的功能和分布与血中的功能和分布明显不同

Joseph A DiDonato¹, Ying Huang, Kulwant S Aulak

¹Departments of Cellular and Molecular Medicine, Lerner Research Institute (J.A.D., Y.H., K.A., G.G., V.G., P.L.F., W.H.W.T., J.D.S., S.L.H.), Cardiovascular Medicine, Heart, and Vascular Institute (W.H.W.T., J.D.S., S.L.H.), and Molecular Cardiology, Lerner Research Institute (E.F.P.), Cleveland Clinic, Cleveland, OH; Department of Medicine, New York University, New York, NY (O.E.-O., E.A.F.); and Departments of Chemistry (G.G., V.G., S.L.H.) and Mathematics (Y.W.), Cleveland State University, Cleveland, OH.

|August 24, 2013

概括

人体动脉中的Apolipoprotein A1 (apoA1) 被氧化和交叉链接,损害了它的功能. 这种动脉壁的ApoA1主要是脂质贫乏的,而不是与HDL相关的,与血不同.

科学领域:

心血管生物学心血管生物学
脂质代谢脂质代谢是什么
动脉样硬化研究动脉样硬化研究

背景情况:

动脉样硬化病变中的Apolipoprotein A1 (apoA1) 是高度氧化的.
氧化apoA1或HDL交叉链接apoA1,损害脂质结合,胆固醇排泄和酶活动.
没有先前的研究量化了apoa1功能或人类动脉壁中的hdl颗粒分布.

研究的目的:

量化从人类动脉壁中恢复的apoA1的功能和HDL颗粒分布.
为了比较动脉样硬化病变中的apoA1特征与正常的大动脉.
为了研究动脉壁的氧化状态和交叉链接apoA1.1.

主要方法:

开发了一种单克隆抗体 (10G1.5) 识别所有形式的apoA1.1.
通过同质体检查了动脉样硬化的斑块负载大动脉中的apoA1丰富.
使用浮力密度分数来确定apoA1粒子分布.
评估了恢复的apoA1.1的功能活动 (胆固醇排放,LCAT).

主要成果:

与正常的大动脉相比,ApoA1在动脉样性大动脉中缩了100倍以上.
大多数 (>90%) 的大动脉apoA1被发现在脂蛋白贫乏分数 (d>1.21),而不是高脂类颗粒 (<3%).
动脉壁 apoA1 (正常和病变) 具有高度交叉连接 (50-70%).
来自大动脉的apoA1表现出比循环的apoA1~80%更低的胆固醇排放量和~90%更低的LCAT活性.

结论:

人类大动脉中的ApoA1与血相比具有不同的功能和分布.
动脉壁 apoA1 充满了动脉样硬化斑块,主要是缺乏脂质,并且没有与高血糖相关.
广泛氧化交叉连接的动脉壁apoA1功能受损.

关键词:

它们是阿波利波蛋白.动脉样硬化症动脉样硬化症心血管疾病心血管疾病斑块,动脉样硬化动脉样硬化

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