Enhanced cardiac mitochondrial biogenesis by nitro-oleic acid remedies diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction

Résumé fourni par la source

Abstract Prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, while treatment options are inadequate. Hypertension and obesity-related metabolic dysfunctions contribute to HFpEF progression. Nitro-oleic acid (NO 2 -OA) impacts metabolic processes by improving glucose tolerance and adipocyte function. In this study, 4 week treatment with NO 2 -OA ameliorated diastolic dysfunction in a HFpEF mouse model induced by high-fat diet and inhibition of the endothelial nitric oxide synthase. A proteomic analysis of left ventricular tissue revealed, that one third of the identified proteins, mostly mitochondrial proteins, were upregulated in hearts of NO 2 -OA-treated HFpEF mice compared to controls and vehicle-treated HFpEF mice, which was confirmed by immunoblot. Activation of the 5’-adenosine-monophosphate-activated-protein-kinase (AMPK) signaling pathway mediated an enhancement of mitochondrial biogenesis in hearts of NO 2 -OA-treated HFpEF mice. In cardiomyocytes under metabolic stress, NO 2 -OA increased mitochondrial protein level accompanied by enhanced oxidative phosphorylation. In conclusion, targeting mitochondrial integrity in HFpEF leads to improved diastolic function.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.