The Effect Of Proliferation,Migration And Phenotypic Modulation Of Smooth Muscle Cells By Platelets Adhesion To Endothelial Cells In Type 2 Diabetes Mellitus

Objective:Diabetic vascular disease is an important chronic complications of diabetes.The diabetic state is often accompanied by endothelial damage or dysfunction and platelets activation,leading to vascular smooth muscle cells(VSMCs)phenotype transformation and increased migration and proliferation,which play a key role in the process of vascular diseases such as atherosclerosis.However,the mechanism of DM2 platelets adhesion to ECs regulating VSMCs phenotypic transformation is still unclear.In this study,we aim to investigate the putative mechanisms of platelets from DM2 adhesion to ECs in regulateing the migration,proliferation and phenotypic modulation of VSMCs.Methods:Mono-and co-cultures of ECs with platelets derived from DM2 for 8 h,then the supernatants were collected for the treatment of VSMCs for 48h.The expression of VSMCs phenotypic switching gene markers were measured by real-time PCR.Cell migration was assessed by scratch assay,and cell proliferation was detected by CCK8 assay.Results:The results showed that platelets from DM2 adhesion to ECs correlated with down-regulation at the mRNA levels of VSMC-specific contractile phenotypic genes(including SM-MHC,Smoothelin-B,SMA,SM22a and contractile regulatory factor SRF)and increased synthetic phenotypic gene expression(including SMemb,CCND1 and CCND2).In addition,platelets from DM2 adhesion to ECs enhanced the migration and proliferation of both ECs and VSMCs.Conclusions:Taken together,these findings illustrated that under diabetic conditions,platelets adhesion to ECs increased the migration and proliferation of both ECs and VSMCs,thus modulated the switching of VSMCs from contractile to synthetic phenotype,and may be associated with cardiovascular complications.