Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex.
Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex.
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DOI：
10.1161/circresaha.108.191361
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发表时间：
2009-02-27
影响因子：
20.1
通讯作者：
Qin X
中科院分区：
文献类型：
--
作者：
Wu G;Hu W;Shahsafaei A;Song W;Dobarro M;Sukhova GK;Bronson RR;Shi GP;Rother RP;Halperin JA;Qin X
补体是免疫系统内的中枢效应子系统，并且涉及一系列炎性病症。CD59是补体膜攻击复合物（MAC）组装的关键调节因子。终末补体致动脉粥样硬化的作用一直被怀疑，但仍不清楚。在这里，我们证明了在载脂蛋白E（Apoe）缺陷的小鼠中，鼠CD59（mCd59ab −/−/Apoe −/−）的额外丢失加速了晚期动脉粥样硬化，其特征为闭塞性冠状动脉粥样硬化、易损斑块和过早死亡，并且这些作用可以通过内皮中人CD59的过度表达而减弱。在mCd59ab −/−/Apoe −/−小鼠中，使用中和抗小鼠C5抗体抑制补体可减弱动脉粥样硬化。此外，MAC介导内皮损伤和促进泡沫细胞形成。这些综合结果突出了MAC的致动脉粥样硬化作用和CD59的动脉粥样硬化保护作用，并表明抑制MAC形成可能为动脉粥样硬化的治疗提供一种治疗方法。
Complement is a central effector system within the immune system and is implicated in a range of inflammatory disorders. CD59 is a key regulator of complement membrane attack complex (MAC) assembly. The atherogenic role of terminal complement has long been suspected, but is still unclear. Here, we demonstrate that among mice deficient in apolipoprotein E (Apoe), the additional loss of murine CD59 (mCd59ab−/−/Apoe−/−) accelerated advanced atherosclerosis featuring occlusive coronary atherosclerosis, vulnerable plaque, and premature death, and that these effect could be attenuated by over-expression of human CD59 in the endothelium. Complement inhibition using a neutralizing anti-mouse C5 antibody attenuated atherosclerosis in mCd59ab−/−/Apoe−/− mice. Furthermore, MAC mediated endothelial damage and promoted foam cell formation. These combined results highlight the atherogenic role of MAC and the athero-protective role of CD59, and suggest that inhibition of MAC formation may provide a therapeutic approach for the treatment of atherosclerosis.