University of Oulu

Ullah K and Wu R (2021) Hypoxia-Inducible Factor Regulates Endothelial Metabolism in Cardiovascular Disease. Front. Physiol. 12:670653. doi: 10.3389/fphys.2021.670653

Hypoxia-inducible factor regulates endothelial metabolism in cardiovascular disease

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Author: Ullah, Karim1; Wu, Rongxue2
Organizations: 1Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
2Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL, United States
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.3 MB)
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Language: English
Published: Frontiers Media, 2021
Publish Date: 2021-10-11


Endothelial cells (ECs) form a physical barrier between the lumens and vascular walls of arteries, veins, capillaries, and lymph vessels; thus, they regulate the extravasation of nutrients and oxygen from the circulation into the perivascular space and participate in mechanisms that maintain cardiovascular homeostasis and promote tissue growth and repair. Notably, their role in tissue repair is facilitated, at least in part, by their dependence on glycolysis for energy production, which enables them to resist hypoxic damage and promote angiogenesis in ischemic regions. ECs are also equipped with a network of oxygen-sensitive molecules that collectively activate the response to hypoxic injury, and the master regulators of the hypoxia response pathway are hypoxia-inducible factors (HIFs). HIFs reinforce the glycolytic dependence of ECs under hypoxic conditions, but whether HIF activity attenuates or exacerbates the progression and severity of cardiovascular dysfunction varies depending on the disease setting. This review summarizes how HIF regulates the metabolic and angiogenic activity of ECs under both normal and hypoxic conditions and in a variety of diseases that are associated with cardiovascular complications.

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Series: Frontiers in physiology
ISSN: 1664-042X
ISSN-E: 1664-042X
ISSN-L: 1664-042X
Volume: 12
Article number: 670653
DOI: 10.3389/fphys.2021.670653
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Funding: RW was supported by the 1R01HL140114-01A1, Chicago DRTC (NIH/P30 DK020595), and CTSA-ITM Core subsidies funding (through NIH UL1 TR000430).
Copyright information: © 2021 Ullah and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.