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Updated: Jun 24, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
CD59 but not DAF deficiency accelerates atherosclerosis in female ApoE knockout mice
Guipeng An1, Takashi Miwa, Wen-Liang Song
1Institute 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.
Insights
CD59, a complement regulator, protects against atherosclerosis in ApoE-deficient mice, particularly in females. DAF deficiency had no significant effect, suggesting CD59
Area of Science:
- Immunology
- Cardiovascular Biology
- Complement System
Background:
- The complement system's role in atherosclerosis is known, but membrane-bound complement regulators' specific influence remains unclear.
- Investigating membrane-bound complement regulators like decay-accelerating factor (DAF) and CD59 is crucial for understanding atherosclerosis pathogenesis.
Purpose of the Study:
- To elucidate the roles of DAF and CD59 in a murine model of atherosclerosis.
- To determine if DAF or CD59 deficiency exacerbates atherosclerosis in apolipoprotein E (ApoE)-deficient mice.
Main Methods:
- Generated DAF(-/-)ApoE(-/-) and CD59(-/-)ApoE(-/-) mice by crossing knockout mice with ApoE-deficient mice.
- Administered a high-fat diet (HFD) for 8 or 16 weeks.
- Assessed lesion extent using en face analysis and aortic root sectioning; performed immunohistochemistry for membrane attack complex (MAC) and collagen.
Main Results:
- CD59 deficiency significantly increased atherosclerotic lesion size in female ApoE(-/-) mice at both 8 and 16 weeks.
- DAF deficiency did not significantly alter atherosclerosis progression in ApoE(-/-) mice.
- CD59 deficiency led to increased MAC deposition and collagen staining, with elevated plasma cholesterol in female mice.
Conclusions:
- CD59, but not DAF, confers protection against atherosclerosis in the context of ApoE deficiency.
- The protective effect of CD59 is gender-biased and likely involves preventing MAC-mediated vascular injury.
- CD59 may also influence plasma cholesterol homeostasis, contributing to its protective role.
Abstract:
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.
