SFB 834:  Endothelial Signalling and Vascular Repair

• Subject Area: Medicine ; Biology
• Term: from 2010 to 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 75732319

Endothelial activation or “dysfunction” is generally accepted to be one of the earliest measurable changes to take place within vessels during cardiovascular disease development and there is a well-documented relationship between attenuated endothelial function and poor patient prognosis. The mechanisms that contribute to the development of endothelial dysfunction have been investigated in detail but the protective molecular mechanisms that maintain the vasculature in a healthy state remain largely elusive. Moreover, it is unclear how endogenous cellular repair mechanisms/processes can improve endothelial cell function and neovascularisation. Our Collaborative Research Centre (hereafter referred to as SFB 834) aims to identify the molecular mechanisms and cellular mediators that determine endothelial cell function and repair in a series of basic science, translational and clinical projects. The overall long-term goal is the development of new therapeutic concepts and their transfer to the clinic. The projects making up SFB 834 are grouped under two general headings: projects in part A: “Endothelial Signaltransduktion”, focus largely on specific signalling molecules and molecular mechanisms that are necessary for the maintenance of endothelial function. The projects in part B “Endothelial Cell Function and Repair” are translational research projects that aim to elucidate the interaction between risk factors (especially those associated with altered cellular metabolism) and endothelial function and to improve the treatment of cardiovascular disease by cell therapy. Several projects focus on the detailed analysis of molecules and established signalling pathways such as nitric oxide, reactive oxygen species, G-protein coupled receptors etc. to gain novel insight into their regulation and participation in cardiovascular disease. However, SFB 834 has a history of identifying emerging priority areas and studying their applicability to vascular research at the basic science and translational research levels. Thus, a subsection of projects focuses on novel mechanisms of epigenetic regulation including regulators of histone modification, microRNAs, long non coding RNAs and RNA splicing. We believe that the elucidation of these novel emerging topics will provide crucial insights into the epigenetic control of cardiovascular diseases, which may lead to the discovery of novel therapeutic targets. It is this focus on the physiology and pathophysiology of the vessel wall and the integration of endothelial cell signalling, vascular repair and translational research that characterises SFB 834.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Signalling pathways mediating endothelial flow sensing and inflammatory activation (Project Heads Offermanns, Stefan ;  Wettschureck, Nina )
• A02 - Metabolic programming of endothelial cells by vascular NADPH oxidases (Project Heads Brandes, Ralf P. ;  Schröder, Ph.D., Katrin )
• A03 - The F-BAR protein NOSTRIN in cardiovascular development and function (Project Head Oess, Stefanie )
• A04 - A Kinase anchoring proteins (AKAPs) in endothelial signalling (Project Heads Fleming, Ph.D., Ingrid ;  Loot, Annemarieke )
• A05 - The effect of AMP-activated protein kinase on endothelial energy metabolism and the consequences for angiogenesis and signalling (Project Heads Fißlthaler, Beate ;  Fleming, Ph.D., Ingrid )
• A06 - Regulation of vascular size and shape by a mechano-responsive transcriptional mechanism (Project Head Potente, Michael )
• A07 - The control of vascular morphogenesis by neuronal guidance cues (Project Head Acker-Palmer, Amparo )
• A08 - Role of Ena/VASP proteins in vessel branching and vascular repair (Project Head Benz, Peter )
• A09 - PYK2-dependent eNOS tyrosine phosphorylation and its role in signalling, disease and repair (Project Head Fleming, Ph.D., Ingrid )
• A10 - The polarity protein Scrib in endothelial cell signalling and angiogenesis (Project Heads Brandes, Ralf P. ;  Michaelis-Popp, U. Ruth )
• A11 - Control of vascular guidance by apelin signalling (Project Heads Helker, Christian ;  Stainier, Ph.D., Didier Y. )
• A12 - G-Protein-coupled receptors in endothelial cells: from single-cell expression to new functions (Project Head Wettschureck, Nina )
• B01 - Regulation of vascular repair and remodelling by non-coding RNAs (Project Heads Dimmeler, Stefanie ;  Fichtlscherer, Stephan ;  Vasa-Nicotera, Mariuca )
• B02 - Function of microRNAs in vascular signalling and repair (Project Head Urbich, Carmen )
• B04 - Fibrin(ogen) degradation products - new endothelial danger signals (Project Head Zacharowski, Ph.D., Kai )
• B05 - Role of JmjC domain-containing proteins in endothelial cell signaling and repair (Project Head Dimmeler, Stefanie )
• B06 - Effect of chronic heart failure on the bone marrow vascular niche (Project Heads Assmus, Birgit ;  Hoffmann, Jedrzej ;  Seeger, Florian H. ;  Zeiher, Andreas Michael )
• B07 - Molecular control of haematopoietic stem cells by the vascular niche (Project Heads Brandts, Christian ;  Serve, Hubert )
• B08 - Regulation of vasculogenic progenitor cells by bone marrow endothelial cells (Project Head Tjwa, Marc )
• B09 - Long non-coding RNAs as regulators of endothelial cell function (Project Head Boon, Reinier )
• B11 - Role of p300/CBP associated factor (PCAF) in endothelial cell signalling (Project Head Gaetano, Carlo )
• B12 - Role of endothelial ADAR1 in vascular growth and homeostasis (Project Head Stellos, Konstantinos )
• B13 - The role of the soluble epoxide hydrolase in the regulation of vascular stability/integrity (Project Head Fleming, Ph.D., Ingrid )
• MGK - Integrated Research Training Unit "Vascular Biology and Medicine" (Project Head Dimmeler, Stefanie )
• Z01 - Quantitative continuous single cell analyses by flow cytometry and video-microscopy-based cell tracking (Project Head Rieger, Michael )
• Z03 - Central Tasks of the Collaborative Research Centre (Project Head Fleming, Ph.D., Ingrid )
• Z04 - Next generation sequencing and bioinformatics platform (Project Head Uchida, Ph.D., Shizuka )

• Applicant Institution: Goethe-Universität Frankfurt am Main
• Participating Institution: Max-Planck-Institut für Herz- und Lungenforschung; W.G. Kerkhoff-Institut
• Spokesperson: Professorin Dr. Ingrid Fleming, Ph.D.