{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:58:59Z","timestamp":1789804739207,"version":"4.0.1"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["P01HL144454"],"award-info":[{"award-number":["P01HL144454"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01ES015024"],"award-info":[{"award-number":["R01ES015024"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["R35HL161244"],"award-info":[{"award-number":["R35HL161244"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["R01HL151680"],"award-info":[{"award-number":["R01HL151680"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Obstructive sleep apnea (OSA) is a common breathing disorder that affects a significant portion of the adult population. In addition to causing excessive daytime sleepiness and neurocognitive effects, OSA is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not completely understood. Using exposure to intermittent hypoxia (IH) to mimic OSA, we have recently reported that mice exposed to IH exhibit endothelial cell (EC) activation, which is an early process preceding the development of cardiovascular disease. Although widely used, IH models have several limitations such as the severity of hypoxia, which does not occur in most patients with OSA. Recent studies reported that mice with deletion of hemeoxygenase 2 (<jats:italic>Hmox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup>), which plays a key role in oxygen sensing in the carotid body, exhibit spontaneous apneas during sleep and elevated levels of catecholamines. Here, using RNA-sequencing we investigated the transcriptomic changes in aortic ECs and heart tissue to understand the changes that occur in <jats:italic>Hmox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice. In addition, we evaluated cardiac structure, function, and electrical properties by using echocardiogram and electrocardiogram in these mice. We found that <jats:italic>Hmox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice exhibited aortic EC activation. Transcriptomic analysis in aortic ECs showed differentially expressed genes enriched in blood coagulation, cell adhesion, cellular respiration and cardiac muscle development and contraction. Similarly, transcriptomic analysis in heart tissue showed a differentially expressed gene set enriched in mitochondrial translation, oxidative phosphorylation and cardiac muscle development. Analysis of transcriptomic data from aortic ECs and heart tissue showed loss of <jats:italic>Hmox2<\/jats:italic> gene might have common cellular network footprints on aortic endothelial cells and heart tissue. Echocardiographic evaluation showed that <jats:italic>Hmox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice develop progressive dilated cardiomyopathy and conduction abnormalities compared to <jats:italic>Hmox2<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> mice. In conclusion, we found that <jats:italic>Hmox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice, which spontaneously develop apneas exhibit EC activation and transcriptomic and functional changes consistent with heart failure.<\/jats:p>","DOI":"10.1371\/journal.pone.0292990","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T17:25:05Z","timestamp":1697477105000},"page":"e0292990","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Loss of heme oxygenase 2 causes reduced expression of genes in cardiac muscle development and contractility and leads to cardiomyopathy in mice"],"prefix":"10.1371","volume":"18","author":[{"given":"Rengul","family":"Cetin-Atalay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo 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