{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:02:58Z","timestamp":1791910978040,"version":"4.3.4"},"reference-count":145,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2020R1A2C1004397"],"award-info":[{"award-number":["2020R1A2C1004397"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["2022R1A2C3005747"],"award-info":[{"award-number":["2022R1A2C3005747"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heme oxygenase (HO) has both beneficial and detrimental effects via its metabolites, including carbon monoxide (CO), biliverdin or bilirubin, and ferrous iron. HO-1 is an inducible form of HO that is upregulated by oxidative stress, nitric oxide, CO, and hypoxia, whereas HO-2 is a constitutive form that regulates vascular tone and homeostasis. In brains injured by trauma, ischemia-reperfusion, or Alzheimer\u2019s disease (AD), the long-term expression of HO-1 can be detected, which can lead to cytotoxic ferroptosis via iron accumulation. In contrast, the transient induction of HO-1 in the peri-injured region may have regenerative potential (e.g., angiogenesis, neurogenesis, and mitochondrial biogenesis) and neurovascular protective effects through the CO-mediated signaling pathway, the antioxidant properties of bilirubin, and the iron-mediated ferritin synthesis. In this review, we discuss the dual roles of HO-1 and its metabolites in various neurovascular diseases, including age-related macular degeneration, ischemia-reperfusion injury, traumatic brain injury, Gilbert\u2019s syndrome, and AD.<\/jats:p>","DOI":"10.3390\/ijms23137041","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T09:00:13Z","timestamp":1656234013000},"page":"7041","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0242-9612","authenticated-orcid":false,"given":"Yoon Kyung","family":"Choi","sequence":"first","affiliation":[{"name":"Bio\/Molecular Informatics Center, Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-7768","authenticated-orcid":false,"given":"Young-Myeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1152\/physiol.00022.2015","article-title":"Oxygen Sensing and Homeostasis","volume":"30","author":"Prabhakar","year":"2015","journal-title":"Physiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1089\/ars.2006.1519","article-title":"Hypoxia-mediated induction of heme oxygenase type I and carbon monoxide release from astrocytes protects nearby cerebral neurons from hypoxia-mediated apoptosis","volume":"9","author":"Imuta","year":"2007","journal-title":"Antioxid. 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