VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol diet
Journal of Lipid Research(2016)
Abstract
Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism. We explored the effect of VNN1 on cholesterol metabolism, inflammation, apoptosis in vitro, and progression of atherosclerotic plaques in apoE(-/-) mice. Oxidized LDL (Ox-LDL) significantly induced VNN1 expression through an ERK1/2/cyclooxygenase-2/PPAR alpha signaling pathway. VNN1 significantly increased cellular cholesterol content and decreased apoAI and HDL-cholesterol (HDL-C)-mediated efflux by 25.16% and 23.13%, respectively, in THP-1 macrophage-derived foam cells (P < 0.05). In addition, VNN1 attenuated Ox-LDL-induced apoptosis through upregulation of expression of p53 by 59.15% and downregulation of expression of B-cell lymphoma-2 127.13% in THP-1 macrophage (P < 0.05). In vivo, apoE(-/-) mice were divided randomly into two groups and transduced with lentivirus (LV)-Mock or LV-VNN1 for 12 weeks. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL-cholesterol (119.64%), TNF-alpha (148.74%), interleukin (IL)-1 beta (131.81%), and IL-6 (156.51%), whereas plasma levels of HDL-C (25.75%) were decreased significantly (P < 0.05). Consistent with these data, development of atherosclerotic lesions was increased significantly upon infection of apoE(-/-) mice with LV-VNN1.(jlr) These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis.-Hu, Y-W., S-G. Wu, J-J. Zhao, X. Ma, J-B. Lu, J-c. Xiu, Y. Zhang, C. Huang, Y-R. Qiu, Y-H. Sha, J-J. Gao, Y-C. Wang, S-F. Li, J-Y. Zhao, L. Zheng, and Q. Wang. VNN1 promotes atherosclerosis progression in apoE(-/-) mice fed a high-fat/high-cholesterol diet.
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Key words
apolipoprotein E,oxidized low density lipoprotein,vanin-1,inflammation
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