Targeting Mitochondrial Metabolic Dysfunction in Pulmonary Hypertension: Toward New Therapeutic Approaches?
Fiche publication
Date publication
mai 2023
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GENY Bernard
Tous les auteurs :
Riou M, Enache I, Sauer F, Charles AL, Geny B
Lien Pubmed
Résumé
Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary vascular remodeling leading to right heart failure and death. To date, despite the three therapeutic approaches targeting the three major endothelial dysfunction pathways based on the prostacyclin, nitric oxide/cyclic guanosine monophosphate, and endothelin pathways, PAH remains a serious disease. As such, new targets and therapeutic agents are needed. Mitochondrial metabolic dysfunction is one of the mechanisms involved in PAH pathogenesis in part through the induction of a Warburg metabolic state of enhanced glycolysis but also through the upregulation of glutaminolysis, tricarboxylic cycle and electron transport chain dysfunction, dysregulation of fatty acid oxidation or mitochondrial dynamics alterations. The aim of this review is to shed light on the main mitochondrial metabolic pathways involved in PAH and to provide an update on the resulting interesting potential therapeutic perspectives.
Mots clés
Warburg effect, metabolic abnormalities, mitochondrial dysfunction, pulmonary hypertension, pulmonary vascular remodeling, right ventricle
Référence
Int J Mol Sci. 2023 05 31;24(11):