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Mol Immunol. 2009 May;46(8-9):1702-9. doi: 10.1016/j.molimm.2009.02.009. Epub 2009 Mar 17.

CD59 but not DAF deficiency accelerates atherosclerosis in female ApoE knockout mice.

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Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Room 1254 BRBII/III, 421 Curie Blvd, Philadelphia, PA 19104, USA.


Although the complement system has been implicated in atherosclerosis, the influence of membrane-bound complement regulators in this process has not been well understood. We studied the role of two membrane complement regulators, decay-accelerating factor (DAF) and CD59, in a murine model of atherosclerosis. DAF(-/-) and CD59(-/-) mice were crossed with apolipoprotein E (ApoE)-deficient mice to generate DAF(-/-)ApoE(-/-) and CD59(-/-)ApoE(-/-) mice. Mice were fed a high fat diet (HFD) for 8 or 16 weeks. En face analysis showed that CD59 deficiency led to more extensive lesions in female ApoE(-/-) mice both at 8 weeks (2.07+/-0.27% vs.1.34+/-0.21%, P=0.06) and 16 weeks (17.13+/-1.14% vs. 9.72+/-1.14%, P<0.001). Similarly, lesions measured by aortic root sectioning were larger in female CD59(-/-)ApoE(-/-) mice than in controls at 8 weeks of HFD feeding (20.74+/-1.33% vs. 13.12+/-1.46%, P<0.005). On the other hand, DAF deficiency did not significantly influence atherosclerosis in ApoE(-/-) mice. Immunohistochemistry revealed more abundant membrane attack complex (MAC) deposition and more collagen staining in the aortic roots of CD59(-/-)ApoE(-/-) mice. Unexpectedly, total plasma cholesterol levels in female CD59(-/-)ApoE(-/-) mice were found to be elevated compared with CD59(+/+)ApoE(-/-) mice. We conclude that CD59 but not DAF offered protection in atherosclerosis in the context of ApoE deficiency. The protective role of CD59 was gender-biased and most likely involved prevention of MAC-mediated vascular injury, with possible contribution from an undefined effect on plasma cholesterol homeostasis.

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