{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T16:58:18Z","timestamp":1771261098555,"version":"3.50.1"},"reference-count":197,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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+, Ca2+, Na+, and Cl\u2212 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.<\/jats:p>","DOI":"10.3390\/biom12040484","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T14:55:35Z","timestamp":1647960935000},"page":"484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Role of Ion Channel Remodeling in Endothelial Dysfunction Induced by Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-4261","authenticated-orcid":false,"given":"Joana","family":"Santos-Gomes","sequence":"first","affiliation":[{"name":"UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6579-6076","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Le Ribeuz","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, School of Medicine, Universit\u00e9 Paris-Saclay, 94276 Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Groupe Hospitalier Paris Saint-Joseph, H\u00f4pital Marie Lannelongue, 92350 Le Plessis-Robinson, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1527-3776","authenticated-orcid":false,"given":"Carmen","family":"Br\u00e1s-Silva","sequence":"additional","affiliation":[{"name":"UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Faculty of Nutrition and Food Sciences, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-6571","authenticated-orcid":false,"given":"Fabrice","family":"Antigny","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, School of Medicine, Universit\u00e9 Paris-Saclay, 94276 Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Groupe Hospitalier Paris Saint-Joseph, H\u00f4pital Marie Lannelongue, 92350 Le Plessis-Robinson, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2203-436X","authenticated-orcid":false,"given":"Rui","family":"Ad\u00e3o","sequence":"additional","affiliation":[{"name":"UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Levitan, P.I., and Dopico, M.D.P.A.M. 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