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

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.

• Authors: Guipeng An, Takashi Miwa, Wen-Liang Song, John A Lawson, Daniel J Rader, Yun Zhang, Wen-Chao Song
• Journal: Molecular immunology (Mol Immunol) Vol. 46 Issue 8-9 Pg. 1702-9 (May 2009) ISSN: 1872-9142 [Electronic] England
• PMID: 19297024 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Apolipoproteins E
• CD55 Antigens
• CD59 Antigens
• Cholesterol

Topics

• Animals
• Aorta (pathology)
• Apolipoproteins E (genetics)
• Atherosclerosis (blood, genetics, pathology)
• CD55 Antigens (genetics, physiology)
• CD59 Antigens (genetics, physiology)
• Cholesterol (blood)
• Disease Progression
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Sex Characteristics
• Time Factors