UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
Faculté de Médecine, School of Medicine, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France.
Biomolecules. 2022 Mar 22;12(4):484. doi: 10.3390/biom12040484.
Endothelial dysfunction is a key player in advancing vascular pathology in pulmonary arterial hypertension (PAH), a disease essentially characterized by intense remodeling of the pulmonary vasculature, vasoconstriction, endothelial dysfunction, inflammation, oxidative stress, and thrombosis in situ. These vascular features culminate in an increase in pulmonary vascular resistance, subsequent right heart failure, and premature death. Over the past years, there has been a great development in our understanding of pulmonary endothelial biology related to the genetic and molecular mechanisms that modulate the endothelial response to direct or indirect injury and how their dysregulation can promote PAH pathogenesis. Ion channels are key regulators of vasoconstriction and proliferative/apoptotic phenotypes; however, they are poorly studied at the endothelial level. The current review will describe and categorize different expression, functions, regulation, and remodeling of endothelial ion channels (K, Ca, Na, and Cl channels) in PAH. We will focus on the potential pathogenic role of ion channel deregulation in the onset and progression of endothelial dysfunction during the development of PAH and its potential therapeutic role.
内皮功能障碍是肺动脉高压（PAH）中血管病理学进展的关键因素，该疾病的特征主要为肺血管的强烈重塑、血管收缩、内皮功能障碍、炎症、氧化应激和原位血栓形成。这些血管特征最终导致肺血管阻力增加、随后的右心衰竭和过早死亡。在过去的几年中，我们对与调节内皮对直接或间接损伤的反应的遗传和分子机制相关的肺内皮生物学有了更深入的了解，以及它们的失调如何促进 PAH 的发病机制。离子通道是血管收缩和增殖/凋亡表型的关键调节剂；然而，它们在内皮水平上的研究还很有限。本综述将描述和分类不同的表达、功能、调节和重构在 PAH 中的内皮离子通道（K、Ca、Na 和 Cl 通道）。我们将重点关注离子通道失调在 PAH 发展过程中内皮功能障碍的发生和进展中的潜在致病作用及其潜在的治疗作用。
