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SFB 834:  Endothelial Signalling and Vascular Repair

Subject Area Medicine
Biology
Term from 2010 to 2021
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 75732319
 
Final Report Year 2022

Final Report Abstract

Diseases of the heart and circulatory system are the most frequent cause of death in Europe (45% of all deaths). Despite the fact that better measures have been developed to decrease and/or manage risk factors, such as hypercholesterolemia and hypertension, coronary artery disease and heart failure are the leading causes of death. Part of the problem is the increased incidence of diabetes and obesity as well as the increasing age of the general population, both of which are positively correlated with cardiovascular disease development. In addition, since most patients now survive a primary cardiovascular event, the proportion of chronic cardiovascular diseases, in particular heart failure is increasing. Endothelial activation or “dysfunction” is generally accepted to be one of the earliest measurable changes to take place within vessels during disease development and there is a well-documented relationship between attenuated endothelial function and poor patient prognosis. Our Collaborative Research Centre (CRC) therefore set out to identify molecular mechanisms and cellular mediators that determine endothelial cell function and repair in a series of translational basic science and clinical projects. The overall long-term goal being the development of new therapeutic concepts and their eventual transfer to the clinic. The main focus of the CRC in the first funding period was on establishing links between specific molecules and endothelial cell function as well as on the impact of different vascular niches and circulating cells for vascular repair. In the second finding period, the CRC picked up on the early reports of the importance of epigenetic regulation and the regulatory role played by microRNAs and long-non coding RNAs in vascular disease and integrated these aspects into basic and translational research projects. The final funding period continued its focus on epigenetic control but also made significant progress in addressing mechanisms underlying the metabolic programing/reprogramming of endothelial cells, endothelial cell diversity and plasticity as well as clonal haematopoiesis of indeterminate potential and the mechanisms determining vascular stability and mural cell coverage. One characteristic of the CRC, throughout all of the funding periods, was the enthusiastic application of state of the art methodologies and the recognition of novel trends from other research areas. This open mindset together with the close collaborative spirit resulted in the widespread use of next generation sequencing as well as proteomic and metabolomics approaches. One consequence was the parallel development of bioinformatics expertise in Frankfurt that benefited the majority of the individual projects.

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