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TRR 23:  Vascular Differentiation and Remodelling

Subject Area Medicine
Biology
Term from 2005 to 2017
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 5486332
 
Final Report Year 2018

Final Report Abstract

Vascular disease directly or indirectly accounts for approximately 70 percent of human deaths and is intimately linked with a number of conditions such as stroke, myocardial infarction, peripheral artery disease, hypertension, rheumatoid arthritis, and cancer as well as the new epidemics of diabetes and obesity. Despite the high social and economic impact of vascular disease, surprisingly little is known about the molecular and cellular mechanisms that affect the cells of the vessel wall during disease development. Moreover, the functional analysis of the molecular mechanisms that regulate blood vessel formation has in the past concentrated on the characterization of pro- and anti-angiogenic molecules that directly act on endothelial cells. This preoccupation with the function of isolated endothelial cells implies that interactions between endothelial cells and other vascular cells, such as pericytes and smooth muscle cells as well as the role of vascular progenitor cells, are not well understood. The Transregional Collaborative Research Centre 23 (SFB-TR23) has studied the vessel wall in health and disease using a variety of state-of-the-art methods, including molecular and cellular biology, vascular physiology, transgenic mice and in-vivo-imaging technology. The work program was divided into three sections. Project area A clustered the projects that concentrated on the role of mediators and effectors that act on vascular cells. Project area B dealt with cellular responses to exogenous stimuli, whereas project area C included projects centered on cellular and systemic interactions between vascular cells and investigated complex regulatory mechanisms in vivo. One basic concept linked all of the projects, namely the notion that the vessel wall is a highly organized multicellular system that requires the interdisciplinary analysis of all of the major cell types involved. The groups of the SFB-TR23 have individually and jointly made seminal discoveries that have shed fundamental insight into vessel wall function and the complexity of vessel wall involvement in maintaining tissue homeostasis as well as adaptation during physiologic and pathologic challenge. Notably, the research pursued within the SFB-TR23 has substantially contributed to a change of paradigm in the field of vascular biology that the vascular endothelium is not merely considered as a responsive cell layer anymore. Instead, being strategically located at the interface between the circulation and the different organs, organotypically differentiated cells of the vessel wall exert gatekeeper functions that actively control their microenvironment through paracrine (‘angiocrine’) acting cytokines. The recognition of the vessel wall as highly dynamic, systemically distributed organ will set the stage for future research in the field of vascular biology for many years to come.

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