{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:07Z","timestamp":1785410527466,"version":"3.56.0"},"reference-count":86,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1201283"],"award-info":[{"award-number":["1201283"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1201283"],"award-info":[{"award-number":["1201283"]}],"id":[{"id":"https:\/\/ror.org\/016nafs32","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Santander Universia","award":["2015"],"award-info":[{"award-number":["2015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-altitude workers in the Los Andes Mountains, known as \u201cthe Chilean miner model,\u201d are exposed to chronic intermittent hypobaric hypoxia (CIHH). This intermittent condition differs from other models of chronic hypoxia, mainly due to the hypoxic pattern and the cardiovascular and pulmonary effects. There are reports of cardiopulmonary dysfunction and remodeling in human and animal models. However, research on some mechanisms of vascular function and the consequences of lung remodeling induced by CIHH is still lacking. Therefore, this study aims to characterize the effects of CIHH exposure on lung structure and redox status in a rat model of the Chilean miner, involving intermittent exposure to chronic cycles of normoxia\/hypobaric hypoxia (96 h\/96 h) in an experimental hypoxic chamber. Our results demonstrate that CIHH acts as a primary driver of pulmonary vascular remodeling by significantly increasing the medial wall thickness of small pulmonary arteries (&lt;100 \u03bcm) and promoting a shift toward a more muscularized phenotype in previously non-muscularized vessels. Structurally, this was characterized by a marked reduction in alveolar space and a significant increase in the thickness of the alveolar-capillary barrier, suggesting impaired gas exchange capacity. These structural changes were strongly associated with a pro-oxidant state, evidenced by increased lipid peroxidation (malondialdehyde levels) and a concomitant reduction in antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase (CAT), in lung tissue. In conclusion, the CIHH model effectively replicates the complex interplay between chronic oxidative damage and structural lung remodeling, identifying the thickening of the arterial medial wall and alveolar septa as key pathological features of probably CIHH-induced pulmonary hypertension.<\/jats:p>","DOI":"10.3390\/ijms27083434","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"3434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lung Vascular Remodeling and Oxidative Damage Induced by Chronic Intermittent Hypoxia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-738X","authenticated-orcid":false,"given":"Esteban G.","family":"Figueroa","sequence":"first","affiliation":[{"name":"Escuela de Obstetricia, Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebasti\u00e1n, Santiago 8420524, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-367X","authenticated-orcid":false,"given":"Alejandro","family":"Gonz\u00e1lez-Candia","sequence":"additional","affiliation":[{"name":"Laboratory of Fetal Neuroprogramming, Institute of Health Sciences, University of O\u2019Higgins, Rancagua 3655000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1726-7559","authenticated-orcid":false,"given":"Alejandro A.","family":"Candia","sequence":"additional","affiliation":[{"name":"Laboratorio de Funci\u00f3n & Reactividad Vascular, N\u00facleo Interdisciplinario de Fisiolog\u00eda, Biof\u00edsica y Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-2748","authenticated-orcid":false,"given":"Adolfo A.","family":"Paz","sequence":"additional","affiliation":[{"name":"Laboratorio de Funci\u00f3n & Reactividad Vascular, N\u00facleo Interdisciplinario de Fisiolog\u00eda, Biof\u00edsica y Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2132-0364","authenticated-orcid":false,"given":"Pamela V.","family":"Arias","sequence":"additional","affiliation":[{"name":"Laboratorio de Funci\u00f3n & Reactividad Vascular, N\u00facleo Interdisciplinario de Fisiolog\u00eda, Biof\u00edsica y Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Rodr\u00edguez-Borges","sequence":"additional","affiliation":[{"name":"Laboratorio de Funci\u00f3n & Reactividad Vascular, N\u00facleo Interdisciplinario de Fisiolog\u00eda, Biof\u00edsica y Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6342-085X","authenticated-orcid":false,"given":"Emilio A.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Laboratorio de Funci\u00f3n & Reactividad Vascular, N\u00facleo Interdisciplinario de Fisiolog\u00eda, Biof\u00edsica y Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"International Center for Andean Studies (INCAS), Universidad de Chile, Putre 1010000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-1326","authenticated-orcid":false,"given":"Rodrigo L.","family":"Castillo","sequence":"additional","affiliation":[{"name":"Laboratorio de Funci\u00f3n & Reactividad Vascular, N\u00facleo Interdisciplinario de Fisiolog\u00eda, Biof\u00edsica y Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Departamento de Medicina Interna Oriente, Facultad de Medicina, Universidad de Chile, Providencia, Santiago 7500922, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.phrs.2015.07.011","article-title":"Pharmacological Approaches in Either Intermittent or Permanent Hypoxia: A Tale of Two Exposures","volume":"101","author":"Herrera","year":"2015","journal-title":"Pharmacol. 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