Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy
Ischemic heart disease (IHD) is a major cause of mortality and morbidity worldwide, with novel therapeutic strategies urgently needed. Endothelial dysfunction is a hallmark of IHD, contributing to its development and progression. Hypoxia-inducible factors (HIFs) are transcription factors activated i...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/7/995 |
| _version_ | 1797590175991201792 |
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| author | Karim Ullah Lizhuo Ai Zainab Humayun Rongxue Wu |
| author_facet | Karim Ullah Lizhuo Ai Zainab Humayun Rongxue Wu |
| author_sort | Karim Ullah |
| collection | DOAJ |
| description | Ischemic heart disease (IHD) is a major cause of mortality and morbidity worldwide, with novel therapeutic strategies urgently needed. Endothelial dysfunction is a hallmark of IHD, contributing to its development and progression. Hypoxia-inducible factors (HIFs) are transcription factors activated in response to low oxygen levels, playing crucial roles in various pathophysiological processes related to cardiovascular diseases. Among the HIF isoforms, HIF2α is predominantly expressed in cardiac vascular endothelial cells and has a key role in cardiovascular diseases. HIFβ, also known as ARNT, is the obligate binding partner of HIFα subunits and is necessary for HIFα’s transcriptional activity. ARNT itself plays an essential role in the development of the cardiovascular system, regulating angiogenesis, limiting inflammatory cytokine production, and protecting against cardiomyopathy. This review provides an overview of the current understanding of HIF2α and ARNT signaling in endothelial cell function and dysfunction and their involvement in IHD pathogenesis. We highlight their roles in inflammation and maintaining the integrity of the endothelial barrier, as well as their potential as therapeutic targets for IHD. |
| first_indexed | 2024-03-11T01:17:45Z |
| format | Article |
| id | doaj.art-8f3122e1416e47e1946a15f7c09ca68e |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T01:17:45Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-8f3122e1416e47e1946a15f7c09ca68e2023-11-18T18:24:06ZengMDPI AGBiology2079-77372023-07-0112799510.3390/biology12070995Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease TherapyKarim Ullah0Lizhuo Ai1Zainab Humayun2Rongxue Wu3Section of Cardiology, Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, USASection of Cardiology, Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, USASection of Cardiology, Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, USASection of Cardiology, Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, USAIschemic heart disease (IHD) is a major cause of mortality and morbidity worldwide, with novel therapeutic strategies urgently needed. Endothelial dysfunction is a hallmark of IHD, contributing to its development and progression. Hypoxia-inducible factors (HIFs) are transcription factors activated in response to low oxygen levels, playing crucial roles in various pathophysiological processes related to cardiovascular diseases. Among the HIF isoforms, HIF2α is predominantly expressed in cardiac vascular endothelial cells and has a key role in cardiovascular diseases. HIFβ, also known as ARNT, is the obligate binding partner of HIFα subunits and is necessary for HIFα’s transcriptional activity. ARNT itself plays an essential role in the development of the cardiovascular system, regulating angiogenesis, limiting inflammatory cytokine production, and protecting against cardiomyopathy. This review provides an overview of the current understanding of HIF2α and ARNT signaling in endothelial cell function and dysfunction and their involvement in IHD pathogenesis. We highlight their roles in inflammation and maintaining the integrity of the endothelial barrier, as well as their potential as therapeutic targets for IHD.https://www.mdpi.com/2079-7737/12/7/995ischemic heart diseaseendothelial cell functionHIF2αARNTHIF pathwayinflammation |
| spellingShingle | Karim Ullah Lizhuo Ai Zainab Humayun Rongxue Wu Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy Biology ischemic heart disease endothelial cell function HIF2α ARNT HIF pathway inflammation |
| title | Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy |
| title_full | Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy |
| title_fullStr | Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy |
| title_full_unstemmed | Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy |
| title_short | Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy |
| title_sort | targeting endothelial hif2α arnt expression for ischemic heart disease therapy |
| topic | ischemic heart disease endothelial cell function HIF2α ARNT HIF pathway inflammation |
| url | https://www.mdpi.com/2079-7737/12/7/995 |
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