کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5946480 1172359 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeted mouse complement inhibitor CR2-Crry protects against the development of atherosclerosis in mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Targeted mouse complement inhibitor CR2-Crry protects against the development of atherosclerosis in mice
چکیده انگلیسی


- Targeted complement inhibitor CR2-Crry treatment resulted in significantly fewer atherosclerotic lesions in mCd59 ab+/+/Apoe−/− mice.
- CR2-Crry inhibited the accelerated atherogenesis seen in mCd59 ab−/−/Apoe−/− mice.
- CR2-Crry treatment reduced C3 and MAC deposition, infiltrating macrophages and T cells in the vasculature of both mice.
- The data demonstrated the therapeutic potential of targeted complement inhibition in prevention/treatment of atherosclerosis.

ObjectiveAtherosclerosis 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.Methods and resultsPrevious 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, mCd59 ab+/+/Apoe−/− and mCd59 ab−/−/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 mCd59 ab+/+/Apoe−/− and mCd59 ab−/−/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.ConclusionThe data demonstrate the therapeutic potential of targeted complement inhibition.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 234, Issue 1, May 2014, Pages 237-243
نویسندگان
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