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 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.
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yan-Wei
YW
Hu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Shao-Guo
SG
Wu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Jing-Jing
JJ
Zhao
Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Xin
X
Ma
Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Jing-Bo
JB
Lu
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Jian-Cheng
JC
Xiu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yuan
Y
Zhang
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Chuan
C
Huang
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yu-Rong
YR
Qiu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yan-Hua
YH
Sha
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Ji-Juan
JJ
Gao
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yan-Chao
YC
Wang
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Shu-Fen
SF
Li
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Jia-Yi
JY
Zhao
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China nfyywangqian@163.com nfyyzl@163.com.
Lei
L
Zheng
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China nfyywangqian@163.com nfyyzl@163.com.
Qian
Q
Wang
D000581:Amidohydrolases / Q000502:physiology*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000201:enzymology* / Q000209:etiology; D018938:Caco-2 Cells; D002788:Cholesterol Esters / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D058851:GPI-Linked Proteins / Q000502:physiology; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000502:physiology; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D001057:Apolipoproteins E; C000595707:BCL2 protein, human; D002788:Cholesterol Esters; D058851:GPI-Linked Proteins; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C099252:oxidized low density lipoprotein; D000581:Amidohydrolases; C022314:pantetheinase
apolipoprotein E; inflammation; oxidized low density lipoprotein; vanin-1