Emiel Van der Vorst (Germany)
RWTH Aachen University
Institute for Molecular Cardiovascular Research (IMCAR)
During my PhD-studies, I especially focussed on the role of HDL in vascular cells and macrophages. After my PhD in 2015, I moved to Munich (Germany) for a postdoctoral research stay in the lab of Prof. Christian Weber. Here, I particularly investigated the role of chemokine receptors in atherosclerosis. Additionally, I was able to obtain personal funding to start my independent line of research focussing on the role of the Calcium-Sensing receptor in atherosclerosis. After moving to Maastricht/Aachen in 2019, I also remained active in Munich as group-leader. The main focus of my research group is Immune-Lipid Crosstalk, combining my expertise obtained during my PhD-studies and Postdoctoral research. Since my start as group leader, I have independently conceived and conceptualised several innovative ideas focussing on the interplay between lipids and immune cells, especially in the context of atherosclerosis, resulting in various grants. Currently, I am also focussing on the interplay between chronic kidney disease and atherosclerosis as part of a recently established research institute called Aachen-Maastricht Cardiorenal Research Institute (AMICARE). Furthermore, we have established novel state-of-the-art techniques in my lab, for example Kinase activity profiling, enabling the measurement of 340 kinases in your sample.

Presenter of 1 Presentation

 Conference Calendar

ENDOTHELIAL ACKR3 DRIVES ATHEROSCLEROSIS BY PROMOTING IMMUNE CELL ADHESION TO VASCULAR ENDOTHELIUM

Session Name
0640 - Endothelial cell biology in atherosclerosis (ID 6)
Session Type
Workshop - Pathogenesis, vascular biology
Date
Tue, 24.05.2022
Session Time
15:45 - 17:15
Room
Anitschkow - Silver Plenary hall
Presenter
Lecture Time
16:45 - 16:55

Abstract

Background and Aims

Genome wide association studies revealed a strong association between the CXCL12 gene locus and cardiovascular diseases, highlighting its receptors CXCR4 and atypical chemokine receptor-3 (ACKR3) as targets for CVD research. Although vascular CXCR4 is well studied in atherosclerosis, the exact role of ACKR3 remains elusive. Therefore, the aim of this project is to decipher the role of vascular ACKR3 in atherosclerosis.

Methods

Vascular endothelium (Bmx-cre) specific Ackr3 deficient mice on Apoe-/- background were fed with a cholesterol-rich diet. Lesions in the aortic roots and arches were analyzed via H&E staining. The phenotype was further characterized employing ex-vivo perfusion and intravital microscopy for cell adhesion and Evans-blue injection for endothelial permeability. Signaling studies are performed in human coronary artery endothelial cells (HCAECs).

Results

Endothelial Ackr3 deficiency resulted in significantly smaller atherosclerotic lesions, accompanied by a more stable plaque phenotypes (more lesional collagen and smooth muscle cell content, smaller necrotic cores). Endothelial-Ackr3-/- mice revealed a reduction in plaque macrophage content and ICAM positive endothelial cells in atherosclerotic lesions. Moreover, immune cell adhesion on carotid arteries lacking endothelial ACKR3 was decreased whilst endothelial permeability was not affected. ACKR3 silencing in TNF-stimulated HCAECs decreased adhesion molecule expression and downregulated MAPK signaling and NF-kB p65 phosphorylation. Endothelial cells in atherosclerotic lesions also revealed decreased phospho-NF-kB p65 expression in Ackr3 deficient mice.

Conclusions

Collectively, our findings indicate that arterial endothelial ACKR3 fuels atherosclerosis by mediating endothelium-immune cell adhesion, most likely through inflammatory MAPK and NF-kB pathways resulting in increased adhesion molecule expression.

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