目的 基于肿瘤内皮标记物 1（TEM1）介导的丝裂原活化蛋白激酶（MAPKs）途径，探讨内皮细胞对血管新生及对心力衰竭心肌重塑的作用。 方法 将小鼠随机分成4组，包括假手术组、MI组、MI+sh-NC组和MI+sh-TEM1组。在心肌梗死（MI）后第7天通过免疫荧光染色检测梗死边缘区EndMT的变化，第28天通过超声心动图评估小鼠的心脏功能。小鼠主动脉内皮细胞（MAECs）分为3组：对照组、Vector组和rTEM1组。此外，用MAPK抑制剂SB203580预处理 MAECs，用rTEM1处理细胞48 h。通过Western blot评估内皮细胞中EndMT和MAPKs信号通路的变化。 结果 在梗死边缘区的心肌中，TEM1水平在MI后第1天轻微增加，在第7天显著达到峰值，然后在第28天降低。与Vector组相比，rTEM1组MAECs中VE-Cadherin蛋白表达显著下降（P < 0.05），和α-SMA、波形蛋白蛋白水平、相对迁移距离、侵袭细胞数和形成分支数量显著增加（P < 0.05）。SB203580逆转了由rTEM1诱导MAECs的这些变化。与MI组相比，MI+sh-TEM1组中的CD31+Vimentin+共染色水平显著降低（P < 0.01）。在第28天，MI+sh-TEM1组小鼠的 LVEF和LVFS均较MI组显著增强（P < 0.05）。与MI组相比，MI+sh-TEM1组小鼠的内皮细胞中p-P38/P38和p-JNK/JNK蛋白表达降低。 结论 TEM1诱导的EndMT和血管生成参与了MI诱导心肌重塑的发病机制，其作用机制与MAPKs信号通路激活有关。

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 groups： sham 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 immunofluorescence staining， and the cardiac function of mice was evaluated by echocardiography on the 28th day. Mouse aortic endothelial cells （MAECs） were divided into three groups： control， 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 significantly （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.