Descrizione del progetto
Approfondimenti sul ruolo della matrice extracellulare nella malattia cardiovascolare
La matrice extracellulare è una vasta rete di proteine e altre molecole che sostiene e organizza le cellule in tessuti nell’organismo. Inoltre, si sta confermando un polo di comunicazione che trasmette gli stimoli meccanici, agevolando l’interazione tra cellule. Il progetto MATRICARD, finanziato dal Consiglio europeo della ricerca, è interessato al ruolo della matrice extracellulare nella malattia cardiovascolare. Pertanto, il gruppo di ricerca analizzerà la composizione della matrice durante condizioni infiammatorie, quali l’arterosclerosi e l’infarto del miocardio, e come può condizionare la progressione della malattia. I risultati del progetto forniranno informazioni importanti sui meccanismi che regolano la matrice extracellulare in condizioni di salute e malattia, individuando al contempo i bersagli terapeutici per prevenire le malattie cardiovascolari.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- social sciencessociologydemographymortality
- medical and health scienceshealth sciencesinflammatory diseases
- medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosis
- medical and health sciencesbasic medicinepathology
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
ERC - Support for frontier research (ERC)Istituzione ospitante
80636 Munich
Germania