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/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.
Highlights
Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism
Recent studies have shown that OxLDL can upregulate expression of Niemann-Pick disease type C1 (NPC1) through the ERK1/2/COX-2/PPAR signaling pathway in macrophages; hepatic VNN1 is under extremely sensitive regulation by PPAR : VNN1 activity in plasma can serve as a reflection of changes in PPAR activity in humans [17, 27]
Our aim was to ascertain if Oxidized LDL (Ox-LDL) upregulates VNN1 expression through the ERK1/2/ COX-2/ PPAR pathway in THP-1 macrophages
Summary
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. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL-cholesterol (119.64%), TNF- (148.74%), interleukin (IL)-1 (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. Atherosclerosis is a multistep process in which apoptosis, lipids, inflammatory cells, and mediators orchestrate the formation and progression of plaques, which can lead to stroke.
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