Mitochondrial ATP production is required for endothelial cell control of vascular tone
Wilson, Calum and Lee, Matthew D. and Buckley, Charlotte and Zhang, Xun and McCarron, John G. (2023) Mitochondrial ATP production is required for endothelial cell control of vascular tone. Function, 4 (2). zqac063. ISSN 2633-8823 (https://doi.org/10.1093/function/zqac063)
Preview |
Text.
Filename: Wilson_etal_Function_2022_Mitochondrial_ATP_production_is_required_for_endothelial_cell_control_of_vascular_tone.pdf
Final Published Version License: Download (10MB)| Preview |
Abstract
Arteries and veins are lined by non-proliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis, rather than mitochondrial oxidative phosphorylation, to fuel each of these energy-demanding processes. However, endothelial metabolism has mainly been studied in the context of proliferative cells, and little is known about energy production in endothelial cells within the fully-formed vascular wall. Using intact arteries isolated from rats and mice, we show that inhibiting mitochondrial respiration disrupts endothelial control of vascular tone. Basal, mechanically-activated, and agonist-evoked calcium activity in intact artery endothelial cells are each prevented by inhibiting mitochondrial ATP synthesis. Agonist-evoked calcium activity was also inhibited by blocking the transport of pyruvate, the master fuel for mitochondrial energy production, through the mitochondrial pyruvate carrier. The role for mitochondria in endothelial cell energy production is independent of species, sex, or vascular bed. These data show that a mitochondrial ATP supply is necessary for calcium-dependent, nitric oxide-mediated endothelial control of vascular tone, and identifies the critical role of endothelial mitochondrial energy production in fueling perfused blood vessel function.
ORCID iDs
Wilson, Calum ORCID: https://orcid.org/0000-0003-2500-0632, Lee, Matthew D. ORCID: https://orcid.org/0000-0001-8265-382X, Buckley, Charlotte ORCID: https://orcid.org/0000-0002-7961-4544, Zhang, Xun ORCID: https://orcid.org/0000-0003-0790-4291 and McCarron, John G. ORCID: https://orcid.org/0000-0002-3302-3984;-
-
Item type: Article ID code: 83463 Dates: DateEvent9 February 2023Published9 December 2022Published Online6 December 2022AcceptedSubjects: Medicine > Pharmacy and materia medica > Pharmaceutical chemistry Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 08 Dec 2022 11:12 Last modified: 04 Dec 2024 01:26 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/83463