B09-Dysregulated extracellular signalling pathways in aortic aneurysm formation in Marfan syndrome and related disorders

We have shown that the structural integrity of the fibrillin microfibril (FMF) scaffold with associated ligands controls biomechanics and cellular behaviour of the aortic wall. Any disturbance of this intricate entity will lead to growth factor dysregulation and aortic disease. In the next funding period, we would like to investigate how the FMF/elastic fibre network regulates and controls the biomechanical properties of collagen in the aorta. We will target and explore degradative mechanisms in the aortic extracellular matrix (ECM) during aortic aneurysm formation. Moreover, we aim to understand how deficiencies in signalling receptors of aortic resident cells translate into structural weakness in the aortic ECM.