Mathew, David;
Davidson, Sean;
Yellon, Derek;
(2025)
HIF-Mediated Fructose Metabolism and Disease Progression in the Cardiovascular-Kidney-Metabolic Syndrome.
Comprehensive Physiology
, 15
(4)
, Article e70033. 10.1002/cph4.70033.
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Abstract
The ‘Cardiovascular-Kidney-Metabolic Syndrome’ which is characterized by multi-organ dysfunction ultimately resulting in adverse cardiac outcomes, serves to highlight the importance of organ crosstalk in pathophysiology. The cellular metabolism of fructose, regulated by Ketohexokinase-C with associated inflammatory sequelae, is mechanistically linked with each component of this clinical entity. Fructose metabolism is confined to the Kidney, Liver, and Small Intestine under normal physiological conditions; however, in the context of ischaemia, HIF-1α induces cardiac expression of Ketohexokinase-C with consequent organ hypertrophy and dysfunction. This adverse effect of cardiac HIF-1α accumulation raises concerns over the potential pleiotropic effects of the ‘HIF stabilizing’ inhibitors of Prolyl Hydroxylase currently entering clinical practice for the treatment of anemia in Chronic Kidney Disease, particularly given the increased cardiovascular mortality observed in this patient group. We suggest that pleiotropic effects of ‘HIF stabilization’ on cardiac physiology warrant investigation and, furthermore, that pharmacological inhibition of Ketohexokinase-C, and therefore fructose metabolism, represents an opportunity to improve cardiac outcomes in the Cardiovascular-Kidney-Metabolic Syndrome.
| Type: | Article |
|---|---|
| Title: | HIF-Mediated Fructose Metabolism and Disease Progression in the Cardiovascular-Kidney-Metabolic Syndrome |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/cph4.70033 |
| Publisher version: | https://doi.org/10.1002/cph4.70033 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Physiology, fructose, HIF, hypoxia, Ketohexokinase, KETOHEXOKINASE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215310 |
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