Abstract
• HIF-1α is activated following myocardial infarction, and is a critical transcription factor promoting survival in hypoxia.
• Type 2 diabetes blunts HIF-1α activation in ischemia and downstream adaptation to hypoxia.
• This effect is mediated by increased long-chain fatty acids, which prevent HIF-1α activation in hypoxia.
• Succinate promotes HIF-1α activation by inhibiting the regulatory HIF hydroxylases. Fatty acids decrease succinate concentrations in hypoxia, by blocking increased glycolysis and malate-aspartate shuttle activity.
• Pharmacologically activating HIF-1α or increasing succinate concentrations restores the hypoxic response and improves functional recovery post-ischemia in diabetes.
• Type 2 diabetes blunts HIF-1α activation in ischemia and downstream adaptation to hypoxia.
• This effect is mediated by increased long-chain fatty acids, which prevent HIF-1α activation in hypoxia.
• Succinate promotes HIF-1α activation by inhibiting the regulatory HIF hydroxylases. Fatty acids decrease succinate concentrations in hypoxia, by blocking increased glycolysis and malate-aspartate shuttle activity.
• Pharmacologically activating HIF-1α or increasing succinate concentrations restores the hypoxic response and improves functional recovery post-ischemia in diabetes.
Original language | English |
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Pages (from-to) | 485-498 |
Number of pages | 14 |
Journal | Journal of the American College of Cardiology: Basic to Translational Science |
Volume | 3 |
Issue number | 4 |
DOIs | |
Publication status | Published - Aug 2018 |
Bibliographical note
NOTICE: this is the author’s version of a work that was accepted for publication inJournal of the American College of Cardiology: Basic to Translational Science
Changes resulting from the publishing process, such as peer review, editing,
corrections, structural formatting, and other quality control mechanisms may not
be reflected in this document. Changes may have been made to this work since it
was submitted for publication. A definitive version was subsequently published in
Journal of the American College of Cardiology: Basic to Translational Science.
© 2018, Elsevier. Licensed under the Creative Commons AttributionNonCommercial-NoDerivatives
4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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Mike Dodd
- Centre for Health and Life Sciences - Assistant Professor Research
Person: Teaching and Research