Cellular Interactions and Heterogeneity in Ischemic Cardiovascular Disease

Cardiovascular disease, and specifically ischemic heart disease, remains the leading cause of death worldwide. Failure of state-of-the-art therapies emphasizes the need for a better understanding of key pathogenetic events in the evolution of the disease that can lead to early identification of individuals at increased risk and to novel therapeutic strategies reducing acute ischemic damage and remodeling towards heart failure in advanced disease. Several risk factors have been identified that, in early stages of the disease, prime the vessels for atherosclerosis and thrombosis, eventually leading to stenosis and episodes of acute ischemia with myocardial infarction. In advanced disease, additional local modifiers of increased mechanical load and ischemia reinforce deleterious remodeling of the heart. None of these processes can be reduced to a single actor and mechanistic insights require diversified, complementary and integrative approaches. The proposed program introduces a novel concept of cellular heterogeneity where depending on prevailing risk factors and disease modifiers, circulating and resident cells in the arterial vessel wall and in the heart adapt a specific molecular footprint, and consequently functional phenotype, in response to local and systemic cues. By doing so, cells further modulate the cardiovascular phenotype in heterocellular cell-cell interactions that reciprocally reinforce disease progression. The overall aim is to explore mechanisms of early and advanced disease within this conceptual framework, to validate findings in patient biosamples, and to initiate translation into clinical diagnostic and ther apeutic practice.

Keywords:Cardiovasculair disease, cell-cell interactions

Disciplines:Laboratory medicine, Cardiac and vascular medicine