755 ATRIAL NATRIURETIC PEPTIDE STIMULATES AUTOPHAGY/MITOPHAGY AND IMPROVES MITOCHONDRIAL DISFUNCTION IN CHRONIC HEART FAILURE

Autor: Giovanna Gallo, Salvatore Raffa, Maurizio Forte, Danilo Ranieri, Simona Marchitti, Damiano Magrì, Marco Testa, Rosita Stanzione, Franca Bianchi, Maria Cotugno, Emiliano Fiori, Vincenzo Visco, Sebastiano Sciarretta, Massimo Volpe, Speranza Rubattu
Rok vydání: 2022
Předmět:
Zdroj: European Heart Journal Supplements. 24
ISSN: 1554-2815
1520-765X
Popis: Background Mitochondrial dysfunction, causing increased reactive oxygen species production, is a molecular feature of heart failure (HF) and it has been reported in circulating leucocytes of patients with HF with reduced ejection fraction (HFrEF). Atrial natriuretic peptide (ANP) exerts many cardiac beneficial effects, including the ability to protect cardiomyocytes by promoting autophagy. Objective To test the impact of ANP on autophagy/mitophagy responses, altered mitochondrial structure and function and increased oxidative stress in chronic HFrEF patients. Experimental design. The present study used both ex-vivo and in-vivo approaches. We examined sixteen consecutive chronic HFrEF patients referring to the outpatient clinic of the Cardiology unit of Sant’Andrea Hospital in Rome. Out of them, for the ex-vivo study we enrolled 10 patients matching the following inclusion criteria: age under 75 years and left ventricle ejection fraction Results The ex-vivo direct exposure to αANP caused an improvement of mitochondrial membrane potential with a restoration of the mitochondrial protonmotive force (p Conclusions αANP stimulates both autophagy and mitophagy responses, counteracts mitochondrial dysfunction and damage ultimately reducing mitochondrial oxidative stress generation in PBMCs from chronic HF patients. These properties were confirmed upon sacubitril/valsartan administration, a therapeutic approach indicated for HFrEF treatment.
Databáze: OpenAIRE