VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol diet
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 t...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-08-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520352123 |
| _version_ | 1819293964327452672 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yan-Wei Hu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T04:18:47Z |
| format | Article |
| id | doaj.art-fac575097ee447b9b06c5d398367dc30 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-24T04:18:47Z |
| publishDate | 2016-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-fac575097ee447b9b06c5d398367dc302022-12-21T17:15:52ZengElsevierJournal of Lipid Research0022-22752016-08-0157813981411VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol dietYan-Wei Hu0Shao-Guo Wu1Jing-Jing Zhao2Xin Ma3Jing-Bo Lu4Jian-cheng Xiu5Yuan Zhang6Chuan Huang7Yu-Rong Qiu8Yan-Hua Sha9Ji-Juan Gao10Yan-Chao Wang11Shu-Fen Li12Jia-Yi Zhao13Lei Zheng14Qian Wang15Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaLaboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaTo whom correspondence should be addressed. (Q.W.); (L.Z.); Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; To whom correspondence should be addressed. (Q.W.); (L.Z.)To whom correspondence should be addressed. (Q.W.); (L.Z.); Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; To whom correspondence should be addressed. (Q.W.); (L.Z.)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.http://www.sciencedirect.com/science/article/pii/S0022227520352123apolipoprotein Eoxidized low density lipoproteinvanin-1inflammation |
| spellingShingle | 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 VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol diet Journal of Lipid Research apolipoprotein E oxidized low density lipoprotein vanin-1 inflammation |
| title | VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol diet |
| title_full | VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol diet |
| title_fullStr | VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol diet |
| title_full_unstemmed | VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol diet |
| title_short | VNN1 promotes atherosclerosis progression in apoE−/− mice fed a high-fat/high-cholesterol diet |
| title_sort | vnn1 promotes atherosclerosis progression in apoe mice fed a high fat high cholesterol diet |
| topic | apolipoprotein E oxidized low density lipoprotein vanin-1 inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520352123 |
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