Mitochondria and Doxorubicin-Induced Cardiomyopathy: A Complex Interplay.

Cardiotoxicity has emerged as a major side effect of doxorubicin (DOX) treatment, affecting nearly 30% of patients within 5 years after chemotherapy. Heart failure is the first non-cancer cause of death in DOX-treated patients. Although many different molecular mechanisms explaining the cardiac derangements induced by DOX were identified in past decades, the translation to clinical practice has remained elusive to date. This review examines the current understanding of DOX-induced cardiomyopathy (DCM) with a focus on mitochondria, which were increasingly proven to be crucial determinants of DOX-induced cytotoxicity. We discuss DCM pathophysiology and epidemiology and DOX-induced detrimental effects on mitochondrial function, dynamics, biogenesis, and autophagy. Lastly, we review the current perspectives to contrast the development of DCM, which is still a relatively diffused, invalidating, and life-threatening condition for cancer survivors.

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

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.

An Overview of the Molecular Mechanisms Associated with Myocardial Ischemic Injury: State of the Art and Translational Perspectives.

Cardiovascular disease is the leading cause of death in western countries. Among cardiovascular diseases, myocardial infarction represents a life-threatening condition predisposing to the development of heart failure. In recent decades, much effort has been invested in studying the molecular mechanisms underlying the development and progression of ischemia/reperfusion (I/R) injury and post-ischemic cardiac remodeling. These mechanisms include metabolic alterations, ROS overproduction, inflammation, autophagy deregulation and mitochondrial dysfunction. This review article discusses the most recent evidence regarding the molecular basis of myocardial ischemic injury and the new potential therapeutic interventions for boosting cardioprotection and attenuating cardiac remodeling.