{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:57:15Z","timestamp":1790740635353,"version":"4.1.0"},"reference-count":141,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009543","name":"Pontificia Universidad Javeriana","doi-asserted-by":"publisher","award":["20539"],"award-info":[{"award-number":["20539"]}],"id":[{"id":"10.13039\/501100009543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary hypertension (PH) is a progressive disorder characterized by elevated pulmonary arterial pressure and the extensive remodeling of pulmonary vasculature. Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), is a well-established contributor to the pathogenesis of PH. OSA is defined by repetitive episodes of upper airway obstruction during sleep, leading to cycles of hypoxia and reoxygenation that trigger a cascade of deleterious events including oxidative stress, inflammation, endothelial dysfunction, and vascular remodeling. Growing evidence underscores the critical role of transient receptor potential canonical (TRPC) channels in mediating hypoxia-induced vascular alterations that contribute to the development of PH. TRPC channels are non-selective cation channels that regulate calcium influx in response to mechanical stimuli, pro-inflammatory cytokines, oxidative stress, and hypoxia. These channels are expressed in both pulmonary arterial smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs), where they modulate key processes such as proliferation, migration, apoptosis, endothelial permeability, and vasoconstriction. Under hypoxic conditions, the upregulation of TRPC1, TRPC3, TRPC4, and TRPC6 has been implicated in dysregulation of calcium homeostasis and activation of pathological signaling pathways that contribute to increased pulmonary arterial pressure. In this review, we propose that upregulation and functional modulation of TRPC channels under CIH represents a central pathogenic mechanism linking OSA to PH. We hypothesize that TRPC1, TRPC3, TRPC4, and TRPC6 act as critical molecular effectors mediating hypoxia-driven calcium influx and downstream signaling pathways that lead to pulmonary vascular remodeling, endothelial dysfunction, and increased pulmonary arterial pressure. This framework allows us to integrate mechanistic insights from molecular, cellular, and translational studies, and to evaluate the therapeutic potential of targeting TRPC channels in OSA-associated PH.<\/jats:p>","DOI":"10.3390\/ijms27041861","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:14:32Z","timestamp":1771236872000},"page":"1861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TRPC Channels as Mediators of Hypoxia-Induced Pulmonary Hypertension in Obstructive Sleep Apnea"],"prefix":"10.3390","volume":"27","author":[{"given":"Yolima P.","family":"Torres","sequence":"first","affiliation":[{"name":"Departamento de Nutrici\u00f3n y Bioqu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3004-4867","authenticated-orcid":false,"given":"Andr\u00e9s Felipe","family":"Aristiz\u00e1bal-Pach\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n y Bioqu\u00edmica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1803-9141","authenticated-orcid":false,"given":"Liliana","family":"Otero","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Odontol\u00f3gicas (CIO), Faculty of Dentistry, Pontificia Universidad Javeriana, Bogot\u00e1 110311, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Humbert, M., Kovacs, G., Hoeper, M.M., Badagliacca, R., Berger, R.M.F., Brida, M., Carlsen, J., Coats, A.J.S., Escribano-Subias, P., and Ferrari, P. 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