Human apolipoprotein A-II protects against diet-induced atherosclerosis in transgenic rabbits.
Human apolipoprotein A-II protects against diet-induced atherosclerosis in transgenic rabbits.
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DOI：
10.1161/atvbaha.112.300445
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Fan J
中科院分区：
文献类型：
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作者：
Wang Y;Niimi M;Nishijima K;Waqar AB;Yu Y;Koike T;Kitajima S;Liu E;Inoue T;Kohashi M;Keyamura Y;Yoshikawa T;Zhang J;Ma L;Zha X;Watanabe T;Asada Y;Chen YE;Fan J
载脂蛋白A-II(apo A-II)是高密度脂蛋白的第二大载脂蛋白，但其在动脉粥样硬化发生发展中的作用尚不清楚。我们的目的是研究载脂蛋白A-II是否在动脉粥样硬化形成中起作用，如果是的话，阐明其中涉及的机制。我们比较了人载脂蛋白A-II转基因(TG)兔和非TG仔兔对高脂饮食诱导的动脉粥样硬化的易感性。在血浆总胆固醇水平相似的情况下，甘油三酯兔的主动脉和冠状动脉粥样硬化的发生率明显低于非甘油三酯兔。TG兔动脉粥样硬化病变以巨噬细胞和平滑肌细胞减少为特征，病变部位常可检测到apoA-II免疫反应蛋白。与非甘油三酯兔相比，甘油三酯兔的血浆C反应蛋白和血白细胞水平较低，甘油三酯兔血浆高密度脂蛋白具有更强的胆固醇外流活性和对巨噬细胞炎性细胞因子表达的抑制作用。此外，TG兔的β-VLDL对铜诱导的氧化反应的敏感性低于非TG兔的β-VLDL。这些结果提示，载脂蛋白A-II在高密度脂蛋白颗粒中的聚集具有动脉粥样硬化保护作用，载脂蛋白A-II可能成为治疗动脉粥样硬化的靶点。
Apolipoprotein A-II (apo A-II) is the second major apolipoprotein of HDLs, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and if so, to elucidate the mechanism involved. We compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells and apo A-II immunoreactive proteins were frequently detected in the lesions. Tg rabbits exhibited low levels of plasma CRP and blood leukocytes compared to non-Tg rabbits and HDLs of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than HDLs isolated from non-Tg rabbits. In addition, β-VLDLs of Tg rabbits were less sensitive to copper-induced oxidation than β-VLDLs of non-Tg rabbits. These results suggest that enrichment of apo A-II in HDL particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis.