Ion channels as convergence points in the pathology of pulmonary arterial hypertension.
Ion channels as convergence points in the pathology of pulmonary arterial hypertension.
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DOI：
10.1042/bst20210538
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发表时间：
2021-08-27
影响因子：
3.9
通讯作者：
Tammaro P
中科院分区：
文献类型：
--
作者：
Jouen-Tachoire TRH;Tucker SJ;Tammaro P
肺动脉高压（PAH）是一种缺乏治愈治疗的心肺系统致命疾病。PAH的主要病理事件是由血管异常收缩和血管重构引起的肺循环血管阻力升高。离子通道是血管平滑肌张力和体内平衡的关键决定因素，目前已经确定了四种PAH通道病变（KCNK3, ABCC8, KCNA5, TRPC6）。然而，离子通道在其他形式的多环芳烃中所起的作用，占多环芳烃患者的大多数，却没有得到很好的表征。在这里，我们推断影响通道功能的多种PAH触发因素（例如BMPR2突变、缺氧、厌食药物）可能有助于疾病的发作。我们回顾了这些“外在”因素聚集在离子通道上并引发其失调以促进多环芳烃发展的分子机制。因此，肺血管的离子通道是有希望的治疗靶点，因为它们可以调节血管舒缩张力和动脉平滑肌细胞的增殖。
Pulmonary arterial hypertension (PAH) is a fatal disease of the cardiopulmonary system that lacks curative treatments. The main pathological event in PAH is elevated vascular resistance in the pulmonary circulation, caused by abnormal vasoconstriction and vascular remodelling. Ion channels are key determinants of vascular smooth muscle tone and homeostasis, and four PAH channelopathies (KCNK3, ABCC8, KCNA5, TRPC6) have been identified so far. However, the contribution of ion channels in other forms of PAH, which account for the majority of PAH patients, has been less well characterised. Here we reason that a variety of triggers of PAH (e.g. BMPR2 mutations, hypoxia, anorectic drugs) that impact channel function may contribute to the onset of the disease. We review the molecular mechanisms by which these ‘extrinsic’ factors converge on ion channels and provoke their dysregulation to promote the development of PAH. Ion channels of the pulmonary vasculature are therefore promising therapeutic targets because of the modulation they provide to both vasomotor tone and proliferation of arterial smooth muscle cells.