{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:54:11Z","timestamp":1790646851757,"version":"4.1.0"},"reference-count":173,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\u2014NIH\/NHLBI Catalyze","award":["R33 HL156141"],"award-info":[{"award-number":["R33 HL156141"]}]},{"name":"Medical Scientist Training Program","award":["NIH T32GM145462"],"award-info":[{"award-number":["NIH T32GM145462"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxia, characterized by insufficient oxygen saturation, triggers a wide array of vascular responses aimed at enhancing cell survival and proliferation. This process is primarily driven by the activation of oxygen-sensing hypoxia-inducible factors (HIFs). HIF-1\u03b1, a key mediator in this context, plays a crucial role in vascular restructuring in response to low oxygen tension and oxygen-independent signaling pathways, making it a promising therapeutic target for ischemic cardiovascular diseases such as peripheral artery disease and coronary artery disease. In this review, we explore both oxygen-dependent and oxygen-independent mechanisms of HIF-1\u03b1 regulation, the role of the HIF protein family in vessel collateralization, and translational efforts to leverage HIF-1\u03b1\u2018s pivotal role in hypoxia signaling for the development of clinical treatments for ischemic cardiovascular disease.<\/jats:p>","DOI":"10.3390\/ijms262211236","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T08:59:46Z","timestamp":1763715586000},"page":"11236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Biological Regulation of HIF-1\u03b1 and Its Role in Therapeutic Angiogenesis for Treatment of Ischemic Cardiovascular Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Ethan","family":"Carmichael","sequence":"first","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4080-7151","authenticated-orcid":false,"given":"Anne-Isabelle S.","family":"Reme","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Bosco","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulexi Y.","family":"Ortiz","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Alexandra","family":"Ramos","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Gomez","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Ngoc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Surgery, The George Washington University School of Medicine and Health Sciences, Washington DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2847-0613","authenticated-orcid":false,"given":"Arash","family":"Bornak","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omaida C.","family":"Velazquez","sequence":"additional","affiliation":[{"name":"DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Department of Radiology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1146\/annurev.cellbio.15.1.551","article-title":"Regulation of Mammalian O2 Homeostasis by Hypoxia-Inducible Factor 1","volume":"15","author":"Semenza","year":"1999","journal-title":"Annu. 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