2026-05-20T03:47:33Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/133432024-09-27T09:28:36Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Menendez-Montes, Ivan
author
Escobar, Beatriz
author
Gomez, Manuel J
author
Albendea-Gomez, Teresa
author
Palacios, Beatriz
author
Bonzon-Kulichenko, Elena
author
Izquierdo-Garcia, Jose Luis
author
Alonso, Ana Vanessa
author
Ferrarini, Alessia
author
Jimenez-Borreguero, Luis J
author
Ruiz-Cabello, Jesus
author
Vazquez, Jesus
author
Martin-Puig, Silvia
funder
Centro Nacional de Investigaciones Cardiovasculares Carlos III (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación La Marató TV3
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Francisco de Vitoria University (España)
funder
Fondation Leducq
funder
Fundación La Caixa
2021-09-02T07:08:32Z
2021-09-02T07:08:32Z
2021-02-19
iScience. 2021; 24(2):102124
10.1016/j.isci.2021.102124
2589-0042
iScience
33665549
http://hdl.handle.net/20.500.12105/13343
HIF1-alpha expression defines metabolic compartments in the developing heart, promoting glycolytic program in the compact myocardium and mitochondrial enrichment in the trabeculae. Nonetheless, its role in cardiogenesis is debated. To assess the importance of HIF1-alpha during heart development and the influence of glycolysis in ventricular chamber formation, herein we generated conditional knockout models of Hif1a in Nkx2.5 cardiac progenitors and cardiomyocytes. Deletion of Hif1a impairs embryonic glycolysis without influencing cardiomyocyte proliferation and results in increased mitochondrial number and transient activation of amino acid catabolism together with HIF2α and ATF4 upregulation by E12.5. Hif1a mutants display normal fatty acid oxidation program and do not show cardiac dysfunction in the adulthood. Our results demonstrate that cardiac HIF1 signaling and glycolysis are dispensable for mouse heart development and reveal the metabolic flexibility of the embryonic myocardium to consume amino acids, raising the potential use of alternative metabolic substrates as therapeutic interventions during ischemic events.
eng
Activation of amino acid metabolic program in cardiac HIF1-alpha-deficient mice.
journal article
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text/plain
ActivationofAminoAcid_2021.pdf.txt