Effetti cardioprotettivi indotti dal condizionamento ischemico: ruolo delle vescicole extracellulari

During myocardial infarction, timely reperfusion is critical to determine the final infarct area and so the overall loss of contractile function of the heart. However, the restoration of blood supply further exacerbate the damages of the previously ischemic heart. This type of injury is known as ischemia-reperfusion injury. Ischemic preconditioning is a technique which consists of brief cycles of ischemia and reperfusion in order to protect the heart against the loss of blood supply. In remote ischemic preconditioning (RIPC) the ischemic insult is applied to distant areas within the heart or distant organs but also limbs. However, how the stimulus of RIPC is transduced from the limb to the ischemic heart is still unknown. Extracellular vesicles (EVs) are lipid bilayer-coated particles secreted by most cell types into the extracellular space and subsequently into the circulation and widely enriched with several bioactive molecules. EVs have been identified as potential mediators of cardioprotective signals of RIPC. In the present study, I investigated the cardioprotective role of RIPC on the hearts of mice undergoing ischemia/reperfusion injury, confirming its cardioprotective effect as reduction of the infarcted area. Moreover, I purified the extracellular vesicles released upon RIPC stimulus and checked for their protective activity in vitro, focusing on the molecular mechanism of action and the characterization of the tissue of origin of the EVs population. Collectively, my thesis provides insights on the cardioprotective mechanism of RIPC in ischemia/reperfusion injury.