Overexpression of complement component C5a accelerates the development of atherosclerosis in ApoE-knockout mice

// Guipeng An 1,2 , Bo Li 1,2 , Xiaoman Liu 1,2 , Mingxiang Zhang 1,2 , Fei Gao 1,2 , Yuxia Zhao 1,2 , Fengshuang An 1,2 , Yun Zhang 1,2 and Cheng Zhang 1,2 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China 2 Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China Correspondence to: Cheng Zhang, email: // Keywords : complement system, atherosclerosis, C5a, Pathology Section Received : October 10, 2015 Accepted : July 06, 2016 Published : August 10, 2016 Abstract Background: In this study, we investigated the direct effect of C5a overexpression on atherosclerosis. Methods and Results: A recombinant adenovirus expressing mouse C5a (Ad-C5a) was constructed and injected intravenously into ApoE -/- mice. After 12 weeks of a high-fat diet, Ad-C5a injection produced more extensive lesions than control adenovirus, and its proathrosclerotic role was significantly blocked by C5a receptor antagonist. Immunohistochemical analysis showed enhanced macrophage infiltration in atherosclerotic regions with C5a overexpression. Trans-well assay revealed C5a receptor-dependent chemotaxis of C5a to macrophages. Furthermore, Ad-C5a overexpression promoted foam cell formation and lipid deposition but reduced collagen content. In addition, with Ad-C5a overexpression, the serum levels of interleukin 6 and tumor necrosis factor α were upregulated. Conclusions: C5a overexpression could accelerate the development of atherosclerosis in ApoE -/- mice by promoting macrophage recruitment, foam cell formation and inflammatory activation. Furthermore, its proatherogetic role is mediated by the C5a receptor.