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SFB 688:  Mechanisms and Imaging of Cell-Cell-Interactions in the Cardiovascular System

Subject Area Medicine
Biology
Term from 2006 to 2017
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 14085162
 
Final Report Year 2018

Final Report Abstract

The cardiovascular system comprises a multitude of cell populations that interact in spatio- and temporal tightly controlled manner to ensure not only the supply of organs with oxygen and nutrients, but also to safeguard inflammation, healing and remodelling processes. The physiological interaction between platelets, inflammatory cells, endothelial cells and other vascular or neighbouring cells is essential for normal haemostasis and the control of vascular barrier function. Disturbances of these cell-cell interactions under pathological conditions can lead to thrombosis, atherosclerosis and inflammation and precipitate cardio- and cerebrovascular diseases, such as myocardial infarction or stroke. The goal of the SFB 688 was therefore to analyse these cell-cell interactions in a translational and interdisciplinary approach by using state of the art imaging techniques, molecular biological methods, and relevant disease models in order to identify novel targets for pharmacological intervention and to develop novel experimental-therapeutical strategies for the (pre)clinical validation of these targets. Research in the SFB 688 focussed on four major areas: (1) Mechanisms underlying intravascular thrombus formation and ischemic/inflammatory processes; (2) Regulation of endothelial barrier function; (3) Cardiovascular signal transduction and regulatory processes and (4) Imaging of cardiovascular cell-cell interactions. A major methodical strength of the SFB 688 was the generation of new transgenic mouse models and their analysis in different disease models (project area A). A second focus comprised the development and application of novel imaging techniques for the dynamic visualization of these experimental disease processes in mice (project area B). We were not only able to elucidate fundamental disease mechanisms, but we also identified and (pre)clinically validated a number of novel potential pharmacological targets, some of which have in the meantime entered clinical trials. Importantly, the work of the SFB 688 formed the basis for a change of paradigm in a central area of the field of cardiovascular research: We were the first to describe the nowadays widely recognized process “thrombo-inflammation” as a fundamental pathomechanism underlying ischemic/inflammatory pathologies and developed first strategies to therapeutically control these processes in experimental disease models. Together, these and further achievements have enabled a better understanding of cardiovascular cell-cell interactions and provided the basis for future research in the field of cardio- and cerebrovascular diseases like for example the new CRC/TR 240 “Platelets” (Würzburg/Tübingen) that commences its work in July 2018.

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