Targeted mouse complement inhibitor CR2-Crry protects against the development of atherosclerosis in mice.
Targeted mouse complement inhibitor CR2-Crry protects against the development of atherosclerosis in mice.
复制标题
DOI：
10.1016/j.atherosclerosis.2014.03.004
复制
发表时间：
2014-05
期刊：
影响因子：
5.3
通讯作者：
Qin, Xuebin
中科院分区：
文献类型：
--
作者：
Liu, Fengming;Wu, Lin;Wu, Gongxiong;Wang, Chun;Zhang, Lining;Tomlinson, Stephen;Qin, Xuebin
动脉粥样硬化是一种慢性炎症和免疫性血管疾病，临床和实验证据表明补体激活产物，包括终末膜攻击复合物（MAC），在动脉粥样硬化形成中的重要作用。在这里，我们研究了补体抑制是否代表使用CR2-Crry（一种最近描述的特异性靶向C3激活位点的补体抑制剂）治疗/预防动脉粥样硬化形成的潜在治疗策略。先前的研究表明，CD 59（MAC形成的膜抑制剂）的丢失加速了Apoe缺陷（Apoe−/−）小鼠的动脉粥样硬化形成。在此，在Apoe缺陷背景下的CD 59充足和CD 59缺陷小鼠（即mCd 59 ab +/+/Apoe−/−和mCd 59 ab −/−/Apoe−/−）分别用CR2-Crry处理4个月和2个月，同时维持高脂肪饮食。与对照治疗相比，CR2-Crry治疗导致主动脉和主动脉根部的动脉粥样硬化病变显著减少，并抑制mCd 59 ab +/+/Apoe−/−和mCd 59 ab −/−/Apoe−/−小鼠中观察到的加速动脉粥样硬化形成。CR2-Crry处理还导致两种小鼠血管系统中C3和MAC沉积显著减少，以及浸润巨噬细胞和T细胞数量显著减少。数据证明了靶向补体抑制的治疗潜力。
Atherosclerosis is a chronic inflammatory and immune vascular disease, and clinical and experimental evidence has indicated an important role of complement activation products, including the terminal membrane attack complex (MAC), in atherogenesis. Here, we investigated whether complement inhibition represents a potential therapeutic strategy to treat/prevent atherogenesis using CR2-Crry, a recently described complement inhibitor that specifically targets to sites of C3 activation. Previous studies demonstrated that loss of CD59 (a membrane inhibitor of MAC formation) accelerated atherogenesis in Apoe deficient (Apoe−/−) mice. Here, both CD59 sufficient and CD59 deficient mice in an Apoe deficient background (namely, mCd59ab+/+/Apoe−/− and mCd59ab−/−/Apoe−/−) were treated with CR2-Crry for 4 and 2 months respectively, while maintained on a high fat diet. Compared to control treatment, CR2-Crry treatment resulted in significantly fewer atherosclerotic lesions in the aorta and aortic root, and inhibited the accelerated atherogenesis seen in mCd59ab+/+/Apoe−/− and mCd59ab−/−/Apoe−/− mice. CR2-Crry treatment also resulted in significantly reduced C3 and MAC deposition in the vasculature of both mice, as well as a significant reduction in the number of infiltrating macrophages and T cells. The data demonstrate the therapeutic potential of targeted complement inhibition.
登录
查看更多内容
DOI：
10.4049/jimmunol.181.11.8068
发表时间：
2008-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Huang Y;Qiao F;Atkinson C;Holers VM;Tomlinson S
通讯作者：
Tomlinson S
影响因子：
--
作者：
Sekine, Hideharu;Kinser, Ting Ting Hsieh;Qiao, Fei;Martinez, Efrain;Paulling, Emily;Ruiz, Phillip;Gilkeson, Gary S.;Tomlinson, Stephen
通讯作者：
Tomlinson, Stephen
影响因子：
4.4
作者：
Atkinson, Carl;Qiao, Fei;Tomlinson, Stephen
通讯作者：
Tomlinson, Stephen
影响因子：
20.1
作者：
Wu G;Hu W;Shahsafaei A;Song W;Dobarro M;Sukhova GK;Bronson RR;Shi GP;Rother RP;Halperin JA;Qin X
通讯作者：
Qin X
影响因子：
82.9
作者：
Huber-Lang, Markus;Sarma, J. Vidya;Ward, Peter A.
通讯作者：
Ward, Peter A.