| Autor: |
Yan-Wei Hu, Shao-Guo Wu, Jing-Jing Zhao, Xin Ma, Jing-Bo Lu, Jian-cheng Xiu, Yuan Zhang, Chuan Huang, Yu-Rong Qiu, Yan-Hua Sha, Ji-Juan Gao, Yan-Chao Wang, Shu-Fen Li, Jia-Yi Zhao, Lei Zheng, Qian Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 57, Iss 8, Pp 1398-1411 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M065565 |
| Popis: |
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/PPARα 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-α (148.74%), interleukin (IL)-1β (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. These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
