Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.
Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.
Int J Mol Sci. 2024 Jun 4;25(11):6180. doi: 10.3390/ijms25116180.
Under different pathophysiological conditions, endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development; however, EndMT is also implicated in the pathogenesis of several genetically determined and acquired diseases, including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases, aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, and cardiac fibrosis. Accordingly, understanding the mechanisms behind the cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy for treating aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and a lack of robust animal models and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.
在不同的病理生理条件下，内皮细胞通过内皮细胞向间充质细胞转化（EndMT）的过程获得间充质细胞样表型，失去内皮表型。在分子水平上，内皮细胞丧失内皮细胞特异性标志物的表达，如 CD31/血小板内皮细胞黏附分子、血管性血友病因子和血管内皮钙黏蛋白，获得间充质细胞标志物的表达，如α-平滑肌肌动蛋白、N-钙黏蛋白、波形蛋白、成纤维细胞特异性蛋白-1 和胶原。EndMT 由许多不同的途径诱导，并通过多种不同且经常冗余的机制在依赖于细胞病理生理状态的情况下以上下文相关的方式进行调节。EndMT 在胚胎发育中起着至关重要的作用，特别是在房室瓣发育中；然而，EndMT 也与几种遗传性和获得性疾病的发病机制有关，包括恶性、心血管、炎症和纤维化疾病。在心血管疾病中，动脉粥样硬化、肺动脉高压、瓣膜疾病、纤维弹性组织增生和心脏纤维化中都报道了异常的 EndMT。因此，了解导致 EndMT 的原因和/或效应的机制，最终靶向 EndMT，似乎是治疗异常 EndMT 相关疾病的一种有前途的策略。然而，这种方法受到缺乏精确的功能和分子途径、原因和/或效应以及缺乏关于不同疾病中 EndMT 的稳健动物模型和人类数据的限制。在这里，我们综述了 EndMT 的不同机制及其在各种心血管疾病中的作用。
