Tumor endothelial markers1 mediate endothelial cell angiogenesis and heart failure myocardial remodeling via MAPKs pathway / 实用医学杂志

ABSTRACT

Objective To explore the role of endothelial cells in angiogenesis and myocardial remodeling in heart failure based on MAPKs pathway mediated by tumor endothelial marker 1(TEM1).Methods Sixty-four mice were equally randomized into four groupssham operation,myocardial infarction(MI),MI+sh-NC and MI+ sh-TEM1.On the 7th day after MI,the changes of EndMT in the infarct border area were detected by immunofluo-rescence staining,and the cardiac function of mice was evaluated by echocardiography on the 28th day.Mouse aortic endothelial cells(MAECs)were divided into three groupscontrol,Vector and rTEM1.In addition,MAECs were pretreated with MAPK inhibitor SB203580,and the cells were treated with rTEM1 for 48 h.The changes of EndMT and MAPKs signaling pathways in endothelial cells were evaluated by Western blot.Results In the myocardium at the border of infarction,the level of TEM1-1 increased slightly on the 1st day after MI,reached the peak on the 7th day,and then decreased on the 28th day.Compared with Vector group,the expression of VE-Cadherin protein in the rTEM1 group decreased significantly(P<0.05),and the levels of α-SMA and vimentin,relative migration distance,the number of invading cells,and the number of branching formation increased signifi-cantly(P<0.05).SB203580 reversed these changes of MAECs induced by rTEM1.Compared with the MI group,the co-staining level of CD31+Vimentin+ in the MI+sh-TEM1 group decreased significantly(P<0.01).On the 28th day,the LVEF and LVFS in the MI+sh-TEM1 group were significantly higher than those in MI group(P<0.05).Compared with the MI group,the expressions of p-P38/P38 and p-JNK/JNK in the endothelial cells of the MI+sh-TEM1 group decreased.Conclusion EndMT and angiogenesis induced by TEM1 participate in the pathogenesis of cardiac fibroblasts induced by MI,which may be mechanically related to the activation of MAPKs signaling pathway.