The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury
Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabi...
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MDPI AG
2022-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/8/1939 |
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| author | Wei Ruan Xinxin Ma In Hyuk Bang Yafen Liang Jochen Daniel Muehlschlegel Kuang-Lei Tsai Tingting W. Mills Xiaoyi Yuan Holger K. Eltzschig |
| author_facet | Wei Ruan Xinxin Ma In Hyuk Bang Yafen Liang Jochen Daniel Muehlschlegel Kuang-Lei Tsai Tingting W. Mills Xiaoyi Yuan Holger K. Eltzschig |
| author_sort | Wei Ruan |
| collection | DOAJ |
| description | Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b receptors. Adenosine receptor activation can lead to metabolic adaptation to enhance ischemia tolerance or dampen myocardial reperfusion injury via signaling events on immune cells. Many studies highlight that clinical strategies to target the hypoxia-adenosine link could be considered for clinical trials. This could be achieved by using pharmacologic HIF activators or by directly enhancing extracellular adenosine production or signaling as a therapy for patients with acute myocardial infarction, or undergoing cardiac surgery. |
| first_indexed | 2024-03-09T10:00:42Z |
| format | Article |
| id | doaj.art-b695d39aec5348bea368b64e69c3b71e |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:00:42Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b695d39aec5348bea368b64e69c3b71e2023-12-01T23:28:02ZengMDPI AGBiomedicines2227-90592022-08-01108193910.3390/biomedicines10081939The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion InjuryWei Ruan0Xinxin Ma1In Hyuk Bang2Yafen Liang3Jochen Daniel Muehlschlegel4Kuang-Lei Tsai5Tingting W. Mills6Xiaoyi Yuan7Holger K. Eltzschig8Department of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADespite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b receptors. Adenosine receptor activation can lead to metabolic adaptation to enhance ischemia tolerance or dampen myocardial reperfusion injury via signaling events on immune cells. Many studies highlight that clinical strategies to target the hypoxia-adenosine link could be considered for clinical trials. This could be achieved by using pharmacologic HIF activators or by directly enhancing extracellular adenosine production or signaling as a therapy for patients with acute myocardial infarction, or undergoing cardiac surgery.https://www.mdpi.com/2227-9059/10/8/1939adenosinehypoxiaCD73CD39Adora2aA2A |
| spellingShingle | Wei Ruan Xinxin Ma In Hyuk Bang Yafen Liang Jochen Daniel Muehlschlegel Kuang-Lei Tsai Tingting W. Mills Xiaoyi Yuan Holger K. Eltzschig The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury Biomedicines adenosine hypoxia CD73 CD39 Adora2a A2A |
| title | The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury |
| title_full | The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury |
| title_fullStr | The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury |
| title_full_unstemmed | The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury |
| title_short | The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury |
| title_sort | hypoxia adenosine link during myocardial ischemia reperfusion injury |
| topic | adenosine hypoxia CD73 CD39 Adora2a A2A |
| url | https://www.mdpi.com/2227-9059/10/8/1939 |
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