Effects Of Chemerin On The Biological Characteristics Of Endothelial Progenitor Cells And The Organ Lesions In Atheroscleroyic Mice

ObjectiveThe role of adipokines in the development of atherosclerosis(AS)has received increasing attention in recent years.We aimed to explore the effects of chemerin on the biological characteristic of human endothelial progenitor cells(EPCs)and investigate its role in the formation of atherosclerosis in ApoE-knockout(ApoE-/-)mice,to further study the molecular mechanisms involved in atherosclerosis.MethodsEPCs were cultured and treated with chemerin together with the specific p38-mitogen-activated protein kinase(p38MAPK)inhibitor SB203580 in a timedose-dependent manner.Flow cytometry and specific fluorescent staining were used to identify the purity of EPCs.We detected changes in migration,adhesion,proliferation and the apoptosis ratio in EPCs by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT),proliferation assay,transwell and flow cytometry.ApoE-/-mice with high-fat-diet induced AS were treated with chemerin and the specific p38 MAPK inhibitor SB203580.Weight was recorded and fasting glucose was measured before sacrifice.Serum and liver lipid indicators were detected,aortic root sections were stained to analyze plaque compositions and properties,and sections of liver,kidney and white adipose tissue(WAT)were stained to analyze abnormal lipid accumulation and the inflammatory response.ResultsThe data showed that chemerin could enhance the adhesion and migration ability of EPCs in a time-dose-dependent manner via the p38 MAPK pathway,and reduce the apoptotic ratio.In vivo study,chemerin could increase the instability of the plaque.Compared with the control group and inhibitor group,ApoE-/-mice treated with chemerin protein had more serious artery stenosis(34.01±3.59%,35.61±6.26% and30.80±3.79% in the control group,chemerin group and inhibitor group,respectively)and a greater lipid content(21.34±12.13%,22.46±4.12% and 20.90±10.88% in the control group,chemerin group and inhibitor group,respectively)in plaque.Besides,there is a decrease in collagen(7.83±1.97%,5.67±1.14% and 7.42±0.60% in the control group,chemerin group and inhibitor group,respectively)although without statistical significance.The accumulation of lipids in the liver and kidney was enhanced by treatment with chemerin,as was the inflammation in the hepatic portal area,and the size of adipocytes also increased after intervention with chemerin.ConclusionsIn conclusion,chemerin could enhance the migration and adhesion ability of human EPCs and reduce the apoptosis ratio.In animals,chemerin could increase the instability of atherosclerotic plaques,exacerbate the occurrence of AS.At the same time,it could cause abnormal lipid accumulation in liver and kidney of ApoE-/-mice.After specifically blocking the p38 MAPK pathway,the effect of chemerin was reduced.