The endothelial-mesenchymal transition (EndMT) plays a key role in the development of cardiac fibrosis (CF) after acute myocardial infarction (AMI). The results of our previous study showed that amphiregulin (AR) expression was enhanced after MI. However, the role of AR on EndMT post MI remains unknown. This study aimed to elucidate the impact of AR on EndMT post MI and the associated molecular mechanisms. AR expression was markedly enhanced in infarct border area post MI, and endothelial cells were one of the primary cell sources of AR secretion. Stimulation with AR promoted endothelial cell proliferation, invasion, migration, collagen synthesis and EndMT. In addition, EGFR and downstream gene expression was significantly enhanced. In vivo, EndMT was significantly inhibited after lentivirus-AR-shRNA was delivered to the myocardium post MI. In addition, silencing AR ameliorated cardiac function by decreasing the extent of CF. Furthermore, the levels of EGFR pathway components in endothelial cells extracted from infarct border myocardium were all significantly decreased in lentivirus-AR-shRNA-treated MI mice. Our results demonstrate that AR induces CF post MI by enhancing EndMT in endothelial cells. Thus, targeting the regulation of AR may provide a potentially novel therapeutic option for CF after MI.

中文翻译：

---

双调蛋白通过内皮细胞中的 EGFR 通路诱导内皮-间质转化，从而促进心肌梗死后的心脏纤维化。

内皮-间质转化 (EndMT) 在急性心肌梗死 (AMI) 后心脏纤维化 (CF) 的发展中起着关键作用。我们之前的研究结果表明，MI 后双调蛋白 (AR) 的表达增强。然而，AR 在 EndMT 后 MI 中的作用仍然未知。本研究旨在阐明 AR 对 MI 后 EndMT 的影响以及相关的分子机制。AR表达在MI后梗死边界区明显增强，内皮细胞是AR分泌的主要细胞来源之一。AR 刺激可促进内皮细胞增殖、侵袭、迁移、胶原合成和 EndMT。此外，EGFR 和下游基因表达显着增强。在体内，将慢病毒-AR-shRNA 递送至 MI 后心肌后，EndMT 受到显着抑制。此外，沉默 AR 通过降低 CF 的程度改善心脏功能。此外，在慢病毒-AR-shRNA 处理的 MI 小鼠中，从梗塞边界心肌提取的内皮细胞中 EGFR 通路成分的水平均显着降低。我们的结果表明，AR 通过增强内皮细胞中的 EndMT 诱导 CF 后 MI。因此，针对 AR 的调节可能为 MI 后 CF 提供一种潜在的新型治疗选择。