Chinese Medicine, 2015, 6, 61-74 Published Online March 2015 in SciRes. http://www.scirp.org/journal/cm http://dx.doi.org/10.4236/cm.2015.61007 How to cite this paper: 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. http://dx.doi.org/10.4236/cm.2015.61007 C5L2 Deficiency Enhances Development of Atherosclerosis in ApoE Knockout Mice Yan Liu 1,2 , Alexandre Fisette 1 , Marc Lapointe 1 , Katherine Cianflone 1* 1 Centre de Recherche de l’Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada 2 Department of Pediatrics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China Email: yan.liu.2@ulaval.ca , alexandre.fisette@criucpq.ulaval.ca , Marc.Lapointe@criucpq.ulaval.ca , * katherine.cianflone@fmed.ulaval.ca Received 12 February 2015; accepted 24 March 2015; published 26 March 2015 Copyright © 2015 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ Abstract Background: The complement system is important in development of atherosclerosis via regula- tion 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 pro- posed that, with DIO feeding, C5L2 deficiency would promote a phenotype that encourages athe- rosclerosis 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 in- creased 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). Conclu- sions: C5L2 disruption worsens glucose and lipid metabolism, increases hepatic and circulating inflammation, and aggravates atherosclerosis. Keywords Atherosclerosis, C5L2, Inflammation, Metabolism, Lipid, Glucose * Corresponding author.