Adaptive immune responses in the wounded heart

Myocardial infarction causes tremendous morbidity, mortality, and economic burden. Despite major technological advances, myocardial repair processes and underlying immune responses are still poorly understood. We have previously demonstrated that myocardial infarction triggers distinct immune responses and that adaptive immunity plays a crucial and unprecedented role in the cardiac repair processes. However, to date, there are no established means to qualitatively assess ongoing myocardial repair processes and predict outcomes. Patients with inadequate healing cannot be identified in time to prevent deterioration of heart function to a critical stage (heart failure). Consequently, we do not know how, when, and in which patients to intervene to restore beneficial repair processes. This project aims to identify immune processes to address these unmet needs. In our joint initiative, we will (1) apply cutting-edge techniques (next generation sequencing) on existing, extensive human biomaterial to identify T-cell signatures discriminating good from poor healers and monitor cardiac healing processes in real-time, and (2) devise immune-based therapeutic interventions to restore beneficial healing. These experiments are a requisite to develop novel diagnostic and therapeutic approaches and ultimately translate them to clinical applicability.