Deficiency of the Complement Regulatory Protein CD59 Accelerates the Development of Diabetes-induced Atherosclerosis in Mice

Abstract Aims 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. Methods 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. Results 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. Conclusions The deficiency of CD59 accelerates the development of diabetic atherosclerosis.