Fiche publication
Date publication
novembre 2024
Journal
Nature cardiovascular research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DUCA Laurent
,
Dr BERQUAND Alexandre
Tous les auteurs :
Murcy F, Borowczyk C, Gourion-Arsiquaud S, Torrino S, Ouahrouche N, Barouillet T, Dussaud S, Couralet M, Vaillant N, Merlin J, Berquand A, Kaikkonen MU, McClelland RL, Tressel W, Stein J, Thorp EB, Bertero T, Barbry P, Bailly-Maitre B, Gautier EL, Karjalainen MK, Kettunen J, Duca L, Shea S, Yvan-Charvet L
Lien Pubmed
Résumé
Metabolic dysregulation, including perturbed glutamine-glutamate homeostasis, is common among patients with cardiovascular diseases, but the underlying mechanisms remain largely unknown. Using the human MESA cohort, here we show that plasma glutamine-glutamate ratio is an independent risk factor for carotid plaque progression. Mice deficient in glutaminase-2 (Gls2), the enzyme that mediates hepatic glutaminolysis, developed accelerated atherosclerosis and susceptibility to catastrophic cardiac events, while Gls2 overexpression partially protected from disease progression. High-throughput transcriptional profiling and high-resolution structural biology imaging of aortas showed that Gls2 deficiency perturbed extracellular matrix composition and increased vessel stiffness. This results from an imbalance of glutamine- and glutamate-dependent cross-linked proteins within atherosclerotic lesions and cellular remodeling of plaques. Thus, hepatic glutaminolysis functions as a potent regulator of glutamine homeostasis, which affects the aortic wall structure during atherosclerotic plaque progression.
Référence
Nat Cardiovasc Res. 2024 11 19;:
