Regulation of the Adaptive Response of Cardiac Cells to Ischemia: Role of Nanovesicles

Ischemic heart disease represents 1 in 4 of total global deaths worldwide. Myocardial intercellular cross-talk regulate simultaneously the tissue homeostasis between neighboring cardiac cells in response to acute or chronic ischemic insult. Different studies have suggested that the heterocellular communication of adult myocardium is mainly based on the release of several free soluble biofactors into the extracellular milieu and on the spreading of different ions through selective channels. In light of these findings, the past few decades have witnessed incessant research aimed at protecting the adult myocardium against ischemic injury, but the development of effective cardioprotection is still a desirable achievement. Nowadays, the rapidly evolving nanoscience is offering the opportunity to tailor new reliable therapeutic targets at ultrastructural level in order to prevent or attenuate the progressive myocardial trimodal response (cell death, matrix degradation and reactive cell hypertrophy) against ischemic injury occurring in infarcted heart. All cardiac cell types release nanovesicles termed “exosomes” (size 40-100 nm), which contain different cargo under normoxic and hypoxic microenvironment. In particular, we and other investigators have demostrated that cardiac fibroblasts and cardiac progenitor cells/stem cells interact with ischemic cardiomyocytes through the release of exosomes. Our review provides current insights into the role of nanovesicles in the modulation of injury and repair responses under ischemic microenvironment.