Mamazhakypov Argen, Lother Achim
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Faculty of Medicine, Interdisciplinary Medical Intensive Care, Medical Center, University of Freiburg, Freiburg im Breisgau, Germany.
Front Cardiovasc Med. 2023 Jan 30;10:1118516. doi: 10.3389/fcvm.2023.1118516. eCollection 2023.
Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling and associated with adverse outcomes. In patients with PH, plasma aldosterone levels are elevated, suggesting that aldosterone and its receptor, the mineralocorticoid receptor (MR), play an important role in the pathophysiology of PH. The MR plays a crucial role in adverse cardiac remodeling in left heart failure. A series of experimental studies from the past few years indicate that MR activation promotes adverse cellular processes that lead to pulmonary vascular remodeling, including endothelial cell apoptosis, smooth muscle cell (SMC) proliferation, pulmonary vascular fibrosis, and inflammation. Accordingly, studies have demonstrated that pharmacological inhibition or cell-specific deletion of the MR can prevent disease progression and partially reverse established PH phenotypes. In this review, we summarize recent advances in MR signaling in pulmonary vascular remodeling based on preclinical research and discuss the potential, but also the challenges, in bringing MR antagonists (MRAs) into clinical application.
肺动脉高压（PH）的特征是肺血管重塑，并与不良后果相关。在PH患者中，血浆醛固酮水平升高，这表明醛固酮及其受体——盐皮质激素受体（MR）在PH的病理生理学中起重要作用。MR在左心衰竭的不良心脏重塑中起关键作用。过去几年的一系列实验研究表明，MR激活会促进导致肺血管重塑的不良细胞过程,包括内皮细胞凋亡、平滑肌细胞（SMC）增殖、肺血管纤维化和炎症。因此，研究表明，MR的药理学抑制或细胞特异性缺失可以预防疾病进展，并部分逆转已确立的PH表型。在本综述中，我们基于临床前研究总结了MR信号在肺血管重塑方面的最新进展，并讨论了将MR拮抗剂（MRAs）应用于临床的潜力和挑战。
