| Background and Objective:Adropin,a novel endogenous bioactive peptide,has the protective effect to vascular endothelium and is inversely related to various risk factors of atherosclerosis?AS?.It is not yet clear whether Adropin affects the progression of AS.The purpose of this study was to investigate the effects of exogenous Adropin on AS progression and its mechanism.Methods:The AS model was established after 16 weeks of high fat diet on8-week-old ApoE-/-mice.They were divided into two groups?n=12?:ApoE-/-Group and Adropin Group.Normal saline?20ml/kg,equal volume with adropin group?and Adropin 0.2mg/kg?10?g/ml?were intraperitoneally injected in the 1st and 2nd week after high fat diet.In addition,12 littermate control wild type C57BL/6J mice were used as the control group.After 16 weeks of high-fat feeding,blood was collected from the inferior vena cava for the detection of four items of blood lipid tests[total cholesterol?TC?,triglyceride?TG?,low density lipoprotein cholesterol?LDL-C?,high-densitylipoproteincholesterol?HDL-C?],interleukin-1??IL-1??and interleukin-10?IL-10?.Oil red O staining was used to analyze the lipid mass in the AS plaque of the aortic root.The intima-media thickness?IMT?and intima/media?I/M?of the thoracoabdominal aorta were measured by HE staining.The expressions of Cluster of Designation?CD?68,Tumor Necrosis Factor?TNF?-?,Monocyte Chemical Chemotactic Factor?MCP?-1 and vascular cell adhesion molecule?VCAM?-1 in aortic roots were detected by immunohistochemistry.In addition,the expression of CD68,MCP-1,VCAM-1,Adropin and Reperfusion Injury Rescue Kinase?RISK?-threonine protein kinase?Akt?,Hippo-yes-associated protein?YAP?and Mitogen-activated Protein Kinase?MAPK?-Jun Nterminal Kinase?JNK?signal pathway in the aortic wall were detected by Western blot.Results:1.The level of serum lipids,IL-1?and IL-10 in ApoE-/-group were significantly higher than those in the control group,while Adropin intervention significantly reversed the above changes:[ApoE-/-group and Adropin group data are as follows:TC:?30.15±4.45?mmol/L vs.?8.96±2.93?mmol/L,TG:?2.96±0.48?mmol/L vs.?1.43±0.24?mmol/L,LDL-C:?7.20±0.44?mmol/L vs.?4.68±0.89?mmol/L,HDL-C:?6.90±1.26?mmol/L vs.?1.76±0.71?mmol/L,all p<0.05;IL-1?:?0.71±0.25?pg/ml vs.?0.25±0.42?pg/ml,IL-10:?93.47±25.80?pg/ml vs.?166.42±47.14?pg/ml,p<0.05,respectively].2.In the control group,no obvious AS formation was observed by oil red O and HE staining but aortic AS was severe in the ApoE-/-group while Adropin intervention significantly reduced the plaque load{plaque area/vascular area:?22.27±0.30?%vs.?41.10±0.87?%,p<0.05;IMT[thoracic aorta:?39.06±1.04??m vs.?187.22±48.16??m,abdominal aorta:?34.17±3.73??m vs.?102.92±13.19??m,p<0.05,respectively)];I/M[thoracic aorta:?0.40±0.01?vs.?2.74±0.27?,abdominal aorta:?0.29±0.04?vs.?1.72±0.33?,p<0.05,respectively)]}.3.Compared with the control group,the ApoE-/-group showed a large increase expression of inflammatory factors:CD68,TNF-?,MCP-1 and VCAM-1 in aortic root,Adropin intervention considerably reduced the expression of the above inflammatory factors.On the contrary,protein Adropin showed a decrease in ApoE-/-group and an increment in Adropin group when compared with the control group.4.As for the signaling pathway protein in aortic,the expression of YAP in ApoE-/-group was decreased,whereas the expression of JNK was increased compared with the control group.Adropin treatment up-regulated YAP and inhibited JNK expression,but had no effect on Akt protein expression.Conclusions:Supplementing exogenous Adropin can reduce blood lipids and prohibit atherosclerotic progression.This effect may be related to Hippo-YAP and MAPK-JNK signaling pathways or inhibition of inflammatory factors. |
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