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TRR 259:  Aortic Disease

Subject Area Medicine
Biology
Term since 2019
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 397484323
 
Aortic disease (AD) is a degenerative affliction of aortic tissue which endangers the integrity of all organ systems and greatly impacts individual life expectancy. Ongoing basic research over the last few years has only begun to unravel the molecular pathophysiology of AD, including the contribution of both resident and non-resident effector mechanisms to AD development. Within the first funding period, project leaders from Bonn, Cologne and Düsseldorf have applied cell biological, immunological, physicomechanical and genetic approaches to substantially improve our understanding of the pathophysiology of AD. In the next funding period, we will further dissect the so far identified non-resident and resident effectors, and we will also continue to search for additional, novel mechanisms in cell culture and animal models to better understand the underlying causes of aortic disease and explore novel diagnostic measures of disease progression and potentially druggable targets. We will investigate non-resident effector cells infiltrating and surrounding aortic tissue, including regulatory T-cells, platelets, macrophages and perivascular adipose cells. We will focus on how they mediate aortic tissue damage on the molecular level and how they orchestrate a pro-inflammatory response through activation and detection of danger signals and physical stimuli such as TLR3, RIG-I, CD40, Sphingosine-1-phosphate and extra-nasal olfactory receptor 2. As resident effectors, the genetic footprints and proteins that drive endothelial heterogeneity in the aortic tissue and intra- and intercellular communication via non-coding RNA and how they induce aortic disease development will be analysed. We will also focus on the molecular events that promote smooth muscle cell fate and phenotype switch and investigate the contribution of extracellular matrix components such as hyaluronan and fibrillin variants to AD and how they interfere with inflammation, growth factors and structural remodelling. Moreover, novel approaches to explicitly translate these findings into organoids, large animal models, and humans have been developed and will be implemented in the upcoming funding period, including longitudinal follow-up of patients with clinical, genetic, imaging, immunological and artificial intelligence analyses to allow prediction of progression from moderate to severe aortic valve disease. The strong, collaborative foundation established by TRR259 has sparked and sustained interdisciplinary research between the sites and institutes, enabling the development of future diagnostic, preventive, and therapeutic strategies, creating new infrastructure, and unifying clinical care and educational programs.
DFG Programme CRC/Transregios
International Connection USA

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Participating University Ruhr-Universität Bochum
 
 

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