CARdiomyocyte-derived extracellular vesicles and inter-organ DIalogue after Myocardial infarction – CARDIM

Cardiovascular diseases, particularly myocardial infarction (MI), remain the leading cause of mortality worldwide. MI triggers an inflammatory response essential for the repair of the damaged myocardium. This inflammatory response is an emergency mechanism involving multiple organs, such as the spleen, and its intensity and duration must be tailored to the initiating stimulus. When excessive, the inflammatory response interferes with cardiac repair and exacerbates the development of heart failure. The mechanisms involved in controlling and adjusting the inflammatory response during MI remain unknown. Understanding molecular mechanisms linking systemic and local inflammation to cardiac repair wil foster the development of novel therapeutic approaches. We have demonstrated that the infarcted heart releases cardiomyocyte-derived extracellular vesicles (CM-EVs), whose pathophysiological role is unknown.
We hypothesize that CM-EVs released by the infarcted heart are crucial mediators of inter-organ communication and shape post-MI inflammatory responses, particularly within the splenic immune cell reservoir. We will address this hypothesis through two complementary aims: 1) We will precisely characterize CM-EVs and map their cell-specific dissemination to remote organs following myocardial infarction, and 2) We will investigate the impact of these CM-EVs on the systemic and local inflammatory responses after MI, focusing on the cardio-splenic axis and analyze how these processes functionally influence ischemic heart repair.