Aging-Related Decline of Autophagy in Patients with Atrial Fibrillation-A Post Hoc Analysis of the ATHERO-AF Study

• Main Authors: Francesco Versaci (Author), Valentina Valenti (Author), Maurizio Forte (Author), Vittoria Cammisotto (Author), Cristina Nocella (Author), Simona Bartimoccia (Author), Leonardo Schirone (Author), Sonia Schiavon (Author), Daniele Vecchio (Author), Luca D'Ambrosio (Author), Giulia Spinosa (Author), Alessandra D'Amico (Author), Isotta Chimenti (Author), Francesco Violi (Author), Giacomo Frati (Author), Pasquale Pignatelli (Author), Sebastiano Sciarretta (Author), Daniele Pastori (Author), Roberto Carnevale (Author)
• Format: Book
• Published: MDPI AG, 2022-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox11040698; 2076-3921
• Keywords: atrial fibrillation; aging; autophagy; cardiovascular disease; oxidative stress; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 11, Iss 4, p 698 (2022)

Background: Aging is an independent risk factor for cardiovascular diseases. The autophagy process may play a role in delaying aging and improving cardiovascular function in aging. Data regarding autophagy in atrial fibrillation (AF) patients are lacking. Methods: A post hoc analysis of the prospective ATHERO-AF cohort study, including 150 AF patients and 150 sex- and age-matched control subjects (CS), was performed. For the analysis, the population was divided into three age groups: <50-60, 61-70, and >70 years. Oxidative stress (Nox2 activity and hydrogen peroxide, H₂O₂), platelet activation (PA) by sP-selectin and CD40L, endothelial dysfunction (nitric oxide, NO), and autophagy parameters (P62 and ATG5 levels) were assessed. Results: Nox2 activity and H₂O₂ production were higher in the AF patients than in the CS; conversely, antioxidant capacity was decreased in the AF patients compared to the CS, as was NO production. Moreover, sP-selectin and CD40L were higher in the AF patients than in the CS. The autophagy process was also significantly impaired in the AF patients. We found a significant difference in oxidative stress, PA, NO production, and autophagy across the age groups. Autophagy markers correlated with oxidative stress, PA, and endothelial dysfunction in both groups. Conclusions: This study provides evidence that the autophagy process may represent a mechanism for increased cardiovascular risk in the AF population.