%0 Journal Article
%T C5L2 Deficiency Enhances Development of Atherosclerosis in ApoE Knockout Mice
%A Yan Liu
%A Alexandre Fisette
%A Marc Lapointe
%A Katherine Cianflone
%J Chinese Medicine
%P 61-74
%@ 2151-1926
%D 2015
%I Scientific Research Publishing
%R 10.4236/cm.2015.61007
%X 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.
%K Atherosclerosis
%K C5L2
%K Inflammation
%K Metabolism
%K Lipid
%K Glucose
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=55062