Projektbeschreibung
Einblicke in die Rolle der extrazellulären Matrix bei Herz-Kreislauf-Erkrankungen
Die extrazelluläre Matrix ist ein großes Netzwerk aus Proteinen und anderen Molekülen, die die Zellen im Körper stützen und zu Geweben organisieren. Die extrazelluläre Matrix entwickelt sich auch zu einem Kommunikationszentrum, das mechanische Reize weiterleitet und die Zell-Zell-Interaktion erleichtert. Das vom Europäischen Forschungsrat finanzierte Projekt MATRICARD befasst sich mit der Rolle der extrazellulären Matrix bei Herz-Kreislauf-Erkrankungen. Die Forschenden werden daher die Zusammensetzung der extrazellulären Matrix bei entzündlichen Erkrankungen wie Atherosklerose und Myokardinfarkt untersuchen und herausfinden, wie sie das Fortschreiten der Krankheit beeinflussen kann. Die Projektergebnisse werden wichtige Erkenntnisse über die Mechanismen liefern, die die extrazelluläre Matrix in Gesundheit und Krankheit regulieren, während die Bestimmung von therapeutischen Zielen dazu beitragen wird, Herz-Kreislauf-Erkrankungen zu verhindern.
Ziel
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.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- social sciencessociologydemographymortality
- medical and health scienceshealth sciencesinflammatory diseases
- medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosis
- medical and health sciencesbasic medicinepathology
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
ERC - Support for frontier research (ERC)Gastgebende Einrichtung
80636 Munich
Deutschland