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Biochem Soc Trans ; 49(4): 1855-1865, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34346486

RESUMO

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.


Assuntos
Canais Iônicos/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Animais , Homeostase , Humanos , Tono Muscular , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Hipertensão Arterial Pulmonar/patologia
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