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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.

KEYWORDS

Atherosclerosis, C5L2, Inflammation, Metabolism, Lipid, Glucose

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. doi: 10.4236-cm.2015.61007.





Autor: Yan Liu1,2, Alexandre Fisette1, Marc Lapointe1, Katherine Cianflone1*

Fuente: http://www.scirp.org/



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