Ricerc@Sapienza

Heart failure (HF) is the end stage of major cardiovascular diseases and a common cause of death and disability worldwide. Several pathogenetic mechanisms contribute to HF development and progression. Among them, recent evidence undercores the mitochondrial dysfunction as one of the most relevant by its ability to increase oxidative stress, reduce ATP production and ultimately accelerate cell damage and death. Mitophagy, an autophagic process devoted to the removal of dysfunctional and damaged mitochondria to allow an adequate cell response to stress stimuli, is reduced in HF.
Natriuretic peptides (NPs) are cardiac hormones that play several beneficial hemodynamic and cellular functions in the cardiovascular system. Among their cellular effects, they stimulate the process of autophagy, in order to remove damaged cells, at both cardiac and vascular level. NPs increase in HF and they help maintain the hemodynamic homeostasis in this condition. It is likely that an enhancement of the cellular effects contributes to explain the protective role of NPs in HF.
A novel class of drug, Angiotensin Receptor Neprilysin inhibitor (ARNi), has been introduced for the treatment of HF patients with reduced systolic function. This drug increases NPs level by reducing their catabolism, therefore enhancing the cardiovascular beneficial properties of these hormones in HF.
Our study will explore the relationship between NPs and preservation of mitochondrial function. In particular, we will analyze: 1) in vitro, the impact of atrial natriuretic peptide on mitochondrial function and mitophagy in circulating leucocytes (PBMCs) of HF patients; 2) in vivo, the impact of increased NPs level upon ARNi treatment on parameters of mitochondrial function and dynamics in HF patients.
Our investigation will reveal novel aspects of the protective function of NPs in HF, and it will provide detailed mechanistic information to explain the beneficial effects of ARNi treatment in HF patients.