Project Details
Projekt
Neutrophils regulate endothelial dysfunction in atherosclerosis (A13#)
Subject Area
Cell Biology
Term
from 2021 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 194468054
The earliest changes that precede the formation of lesions of atherosclerosis take place in the endothelium. These changes include increased endothelial permeability to lipoproteins and other plasma constituents and the up-regulation of endothelial adhesion molecules thus promoting migration of leukocytes into the artery wall. Previous work of the applicant has revealed the importance of neutrophils during early stage atherosclerosis with a focus on neutrophil-driven recruitment of monocytes. Here, we will systematically study how neutrophils alter endothelial fate and function during hyperlipidemia-and ageing-driven atherosclerosis. Specifically, in aim (I) we will assess determinants of the arterial neutrophil-endothelial interplay in atherosclerosis including neutrophil protein composition and neutrophil-endothelial interactions. Furthermore, in aim (II) we will use single cell RNAseq of aortic endothelial cells derived from atherosclerotic mice with intact white blood count or with induced neutropenia to define the global effect of neutrophils on endothelial cell activity. These studies will be made in hyperlipidemic as weil as in aged mice to define the contribution of neutrophils under these conditions. In addition, we will generate an unbiased neutrophil-endothelial interactome by making use of neutrophils carrying SILAC-labeled proteins. Finally, in aim (III) we will target individual neutrophil proteins or groups of neutrophil-derived proteins to alleviate endothelial activation and possibly atherosclerosis development.
DFG Programme
Collaborative Research Centres
Applicant Institution
Universität Münster
Project Head
Professor Dr. Oliver Söhnlein
