The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis
Hypoxia results in a wide range of adaptive physiological responses, including metabolic reprogramming, erythropoiesis, and angiogenesis. The response to hypoxia at the cellular level is mainly regulated by hypoxia-inducible factors (HIFs): HIF1α and HIF2α isoforms. Although structurally similar and...
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2025-05-01
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| author | Mouayad Zuheir Bakleh Ayman Al Haj Zen |
| author_facet | Mouayad Zuheir Bakleh Ayman Al Haj Zen |
| author_sort | Mouayad Zuheir Bakleh |
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| description | Hypoxia results in a wide range of adaptive physiological responses, including metabolic reprogramming, erythropoiesis, and angiogenesis. The response to hypoxia at the cellular level is mainly regulated by hypoxia-inducible factors (HIFs): HIF1α and HIF2α isoforms. Although structurally similar and overlapping gene targets, both isoforms can exhibit distinct expression patterns and functions in some conditions of hypoxia. The interaction between these isoforms, known as the “HIF switch”, determines their coordinated function under varying oxygen levels and exposure time. In angiogenesis, HIF-1α is rapidly stabilized under acute hypoxia, prompting a metabolic shift from oxidative phosphorylation to glycolysis and initiating angiogenesis by activating endothelial cells and extracellular matrix remodeling. Conversely, HIF-2α regulates cell responses to chronic hypoxia by sustaining genes critical for vascular remodeling and maturation. The current review highlights the different roles and regulatory mechanisms of HIF-1α and HIF-2α isoforms, focusing on their involvement in cell metabolism and the multi-step process of angiogenesis. Tuning the specific targeting of HIF isoforms and finding the right therapeutic window is essential to obtaining the best therapeutic effect in diseases such as cancer and vascular ischemic diseases. |
| format | Article |
| id | doaj-art-63f529bb191f4e39b4814497b8e541e2 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-63f529bb191f4e39b4814497b8e541e22025-08-20T01:49:14ZengMDPI AGCells2073-44092025-05-0114967310.3390/cells14090673The Distinct Role of HIF-1α and HIF-2α in Hypoxia and AngiogenesisMouayad Zuheir Bakleh0Ayman Al Haj Zen1College of Health and Life Sciences, Hamad Bin Khalifa University, Doha P.O. Box 34110, QatarCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha P.O. Box 34110, QatarHypoxia results in a wide range of adaptive physiological responses, including metabolic reprogramming, erythropoiesis, and angiogenesis. The response to hypoxia at the cellular level is mainly regulated by hypoxia-inducible factors (HIFs): HIF1α and HIF2α isoforms. Although structurally similar and overlapping gene targets, both isoforms can exhibit distinct expression patterns and functions in some conditions of hypoxia. The interaction between these isoforms, known as the “HIF switch”, determines their coordinated function under varying oxygen levels and exposure time. In angiogenesis, HIF-1α is rapidly stabilized under acute hypoxia, prompting a metabolic shift from oxidative phosphorylation to glycolysis and initiating angiogenesis by activating endothelial cells and extracellular matrix remodeling. Conversely, HIF-2α regulates cell responses to chronic hypoxia by sustaining genes critical for vascular remodeling and maturation. The current review highlights the different roles and regulatory mechanisms of HIF-1α and HIF-2α isoforms, focusing on their involvement in cell metabolism and the multi-step process of angiogenesis. Tuning the specific targeting of HIF isoforms and finding the right therapeutic window is essential to obtaining the best therapeutic effect in diseases such as cancer and vascular ischemic diseases.https://www.mdpi.com/2073-4409/14/9/673hypoxiaHIF signalingHIF switchangiogenesis |
| spellingShingle | Mouayad Zuheir Bakleh Ayman Al Haj Zen The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis Cells hypoxia HIF signaling HIF switch angiogenesis |
| title | The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis |
| title_full | The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis |
| title_fullStr | The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis |
| title_full_unstemmed | The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis |
| title_short | The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis |
| title_sort | distinct role of hif 1α and hif 2α in hypoxia and angiogenesis |
| topic | hypoxia HIF signaling HIF switch angiogenesis |
| url | https://www.mdpi.com/2073-4409/14/9/673 |
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