Deficiency of the complement regulatory protein CD59 accelerates the development of diabetes-induced atherosclerosis in mice.
Deficiency of the complement regulatory protein CD59 accelerates the development of diabetes-induced atherosclerosis in mice.
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DOI：
10.1016/j.jdiacomp.2016.08.021
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发表时间：
2017-02
影响因子：
3
通讯作者：
Halperin JA
中科院分区：
文献类型：
--
作者：
Liu F;Sahoo R;Ge X;Wu L;Ghosh P;Qin X;Halperin JA
临床和实验证据支持补体系统、补体调节蛋白和糖尿病血管并发症的发病机制之间的强有力联系。我们以前报道过，补体调节蛋白CD 59在糖尿病患者中被糖化失活。本研究的目的是通过实验评估CD 59缺乏如何影响体内糖尿病动脉粥样硬化的发展。我们将mCD 59充足和缺陷小鼠与Apoe-/-背景杂交，产生mCD 59 ab +/+/Apoe-/-和mCD 59 ab-/-/Apoe-/-小鼠，并通过多次低剂量注射链脲佐菌素诱导糖尿病。用苏木精-伊红（H&E）和油红-O染色检测动脉粥样硬化。免疫组化检测细胞膜攻击复合物（MAC）沉积和巨噬细胞浸润。糖尿病mCD 59缺陷（mCD 59 ab −/−/ApoE−/−）小鼠的主动脉粥样硬化病变面积扩大了近100（7.5% ± 0.6 vs 3.6% ± 0.7; p < 0.005）和主动脉根部（H&E：26.2% ± 1.9 vs. 14.3% ± 1.1; p < 0.005），两种情况均与血脂升高相关（油红-O：14.9% ± 1.1对比7.8% ± 1.1; p < 0.05）和MAC沉积（6.8% ± 0.8 vs. 3.0% ± 0.7; p <0.005）和巨噬细胞浸润（31.5% ± 3.7 vs. 16.4% ± 3.0; p <0.05），与糖尿病mCD 59充足（mCD 59 ab +/+/ApoE−/−）对应物相比。CD 59的缺乏加速了糖尿病动脉粥样硬化的发展。
Clinical and experimental evidence supports a strong link between the complement system, complement regulatory proteins and the pathogenesis of diabetes vascular complications. We previously reported that the complement regulatory protein CD59 is inactivated by glycation in humans with diabetes. Our objective for this study is to assess experimentally how the deficiency of CD59 impacts the development of diabetic atherosclerosis in vivo. We crossed mCD59 sufficient and deficient mice into the ApoE−/− background to generate mCd59ab+/+/ApoE−/− and mCd59ab−/−/ApoE−/− mice, and induced diabetes by multiple low dose injections of streptozotocin. Atherosclerosis was detected by hematoxylin and eosin (H&E) and oil red-O staining. Membrane attack complex (MAC) deposition and macrophage infiltration were detected by immunostaining. Diabetic mCD59 deficient (mCD59ab−/−/ApoE−/−) mice developed nearly 100% larger atherosclerotic lesion areas in the aorta (7.5% ± 0.6 vs 3.6% ± 0.7; p < 0.005) and in the aortic roots (H&E: 26.2% ± 1.9 vs. 14.3% ± 1.1; p < 0.005), in both cases associated with increased lipid (Oil red-O: 14.9% ± 1.1 vs. 7.8% ± 1.1; p < 0.05) and MAC deposition (6.8% ± 0.8 vs. 3.0% ± 0.7; p <0.005) and macrophage infiltration (31.5% ± 3.7 vs. 16.4% ± 3.0; p <0.05) in the aortic roots as compared to their diabetic mCD59 sufficient (mCD59ab+/+/ApoE−/−) counterpart. The deficiency of CD59 accelerates the development of diabetic atherosclerosis.