Ricerc@Sapienza

Ischaemic heart disease leads to maladaptive remodelling and progressive heart failure (HF). Among interstitial and stromal myocardial cells, a population of primitive cardiac stromal cells (CSCs) play a primary role in cardiac homeostasis, injury, and repair. These cells condition tissue architecture and niche microenvironment mainly through indirect paracrine action. Autophagy is an intracellular degradation process of damaged components that can be cytoprotective or trigger cell death. In the heart, autophagy is an essential process responsible for turnover of organelles, which is dramatically upregulated in response to stress, such as ischemia/reperfusion, and in cardiovascular diseases. Stress conditions may dramatically hamper the survival and cardiogenic phenotype of CSCs. Interestingly, the role of autophagy in the regulation of CSC phenotype and secretome, and in the balance of their cardiogenic versus fibrotic polarization, has never been investigated. The present project proposal aims to: 1) investigate in vitro the effects of autophagy modulation (genetic or pharmacological) on CSC viability and phenotype; 2) investigate in vitro the effects of autophagy activation on CSC secretome under nutrient deprivation condition. The expected results will shed new light on the role of autophagy in CSC phenotypic control and paracrine potential, as a significant mechanism in tissue homeostasis and a potential target for regenerative medicine protocols.