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. 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. Finally, in aim (III) we will neutralize neutrophil-derived proteins to alleviate endothelial activation and possibly atherosclerosis development.
Prof. Dr. Dr. med. Oliver Söhnlein
Funding period: July 2021 - June 2024