The extracellular matrix as a mediator of cell-cell communication in cardiovascular inflammation

ongoing

Cardiovascular diseases, as coronary artery disease (CAD) and its sequelae myocardial infarction (MI) and heart failure, represent the leading cause of morbidity and mortality in industrialized and developing countries. Atherosclerosis is the pathology causing CAD and MI; both are characterized by a sterile inflammation with a chronic and acute course of the disease, respectively. There is a plethora of cell types, as leukocytes, endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, and cardiomyocytes, which play important roles in the initiation, propagation, and termination of the pathophysiological processes. Recent data from genetic studies found that genetic variation influencing extracellular matrix (ECM) proteins is associated with cardiovascular diseases. We found that such proteins which are secreted by one cell type influence phenotypes of other cell types via, e.g., silencing of inflammatory functions or modulation of ECM composition. The ECM hence not only represents a meshwork in which cells are organized but also a communication hub to transduce mechanical stimuli and cell-cell-interaction signals. Here, we aim to explore the ECM proteome in sterile inflammatory diseases as atherosclerosis and MI in an unprecedented depth. We aim to identify novel regulators which give insights into the underlying processes and we will study the molecular and cellular mechanisms modifying the course of the disease. This will lead to the identification of novel therapeutic targets which might reshape our understanding of how these diseases occur and how we can prevent them, and to the development of novel, individualized treatment strategies. Finally, we aim to translate our findings to humans to get first insights on whether these strategies can be adapted and used in clinical trials. MATRICARD will go beyond technical boundaries and lead to a deep knowledge of ECM-mediated cell-cell-communication and reveal its translational potential.