Author(s)

Yan Liu^1,2, Alexandre Fisette¹, Marc Lapointe¹, Katherine Cianflone^1*

¹Centre de Recherche de l’Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada.
²Department of Pediatrics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Background: The complement system is important in development of atherosclerosis via regulation of lipid and glucose metabolism as well as inflammation. Aim: The aim of the present study was to further analyze the contribution of C5L2 to the development of atherosclerosis. We proposed that, with DIO feeding, C5L2 deficiency would promote a phenotype that encourages atherosclerosis development. Coupled to ApoE deficiency, double knockout (2KO) mice would show exacerbated atherosclerotic plaque formation. Methods: First, Wildtype (WT) and C5L2-/-(C5L2KO) and subsequently, ApoE-/-(ApoEKO) and C5L2/ApoE double knockout mice were placed on diets inducing obesity (DIO) or standard chow diet for 12 - 15 weeks. Plasma lipids, glucose, cytokines and hepatic glycogen and lipid contents, mRNA levels and enzyme activities and atherosclerotic plaque size were measured. Results: C5L2KO had increased hepatic glucose oxidation (+90%, p < 0.001), reduced liver glycogen content on chow diet (-34%, p < 0.05) but increased with DIO (+51%, p < 0.05) vs WT. Glucose clearance was delayed in C5L2/ApoE-2KO vs ApoEKO mice with chow (p < 0.0001) and DIO diet (p = 0.0026). C5L2KO mice had increased hepatic lipid content and fatty acid synthesis but decreased lipid oxidation vs WT. Plasma cholesterol was further elevated in C5L2/ApoE-2KO vs ApoEKO with DIO feeding (p < 0.05). Hepatic cytokine expression was increased in C5L2KO mice compared to WT mice. Atherosclerotic plaque size was increased in C5L2/ ApoE-2KO mice compared with apoEKO on chow (p < 0.05) and DIO regimen (p < 0.001). Conclusions: C5L2 disruption worsens glucose and lipid metabolism, increases hepatic and circulating inflammation, and aggravates atherosclerosis.

Atherosclerosis, C5L2, Inflammation, Metabolism, Lipid, Glucose

Liu, Y. , Fisette, A. , Lapointe, M. and Cianflone, K. (2015) C5L2 Deficiency Enhances Development of Atherosclerosis in ApoE Knockout Mice. Chinese Medicine, 6, 61-74. doi: 10.4236/cm.2015.61007.