State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Int J Mol Sci. 2023 Jun 16;24(12):10206. doi: 10.3390/ijms241210206.
Pulmonary hypertension (PH) is a disease which affects the cardiopulmonary system; it is defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as measured by right heart catheterization at rest, and is caused by complex and diverse mechanisms. In response to stimuli such as hypoxia and ischemia, the expression and synthesis of endothelin (ET) increase, leading to the activation of various signaling pathways downstream of it and producing effects such as the induction of abnormal vascular proliferation during the development of the disease. This paper reviews the regulation of endothelin receptors and their pathways in normal physiological processes and disease processes, and describes the mechanistic roles of ET receptor antagonists that are currently approved and used in clinical studies. Current clinical researches on ET are focused on the development of multi-target combinations and novel delivery methods to improve efficacy and patient compliance while reducing side effects. In this review, future research directions and trends of ET targets are described, including monotherapy and precision medicine.
肺动脉高压（PH）是一种影响心肺系统的疾病；它被定义为在休息时通过右心导管测量的平均肺动脉压（mPAP）> 20mmHg，由复杂和多样化的机制引起。在缺氧和缺血等刺激下，内皮素（ET）的表达和合成增加，导致其下游的各种信号通路被激活，并在疾病发展过程中产生诱导异常血管增殖等效应。本文综述了内皮素受体及其通路在正常生理过程和疾病过程中的调节，并描述了目前在临床研究中批准和使用的 ET 受体拮抗剂的作用机制。目前对 ET 的临床研究集中在多靶点组合和新型给药方法的开发上，以提高疗效和患者依从性，同时降低副作用。在这篇综述中，描述了 ET 靶点的未来研究方向和趋势，包括单药治疗和精准医学。
