Most blood vessels are surrounded by perivascular adipose tissue (PVAT) which has a complex bidirectional relationship with vascular walls. Dysfunctional PVAT plays a role in the pathogenesis of atherosclerosis due to infiltration of proatherogenic immune cells into PVATs through the adventitia that is a gateway for macrophage and leukocyte migration. The subsequent low-grade inflammatory state in PVAT leads to tissue remodelling and is accompanied by phenotype switching of adipose tissue macrophages (ATMs) from anti-inflammatory ‘M2’ to pro-inflammatory ‘M1’phenotype. The receptor ChemR23 and its ligand chemerin seem to play a crucial role in M1/M2 polarization and thus in the crosstalk between PVAT and arteries during atherosclerosis.

We use an atherosclerotic mouse model with a systemic knockout of ChemR23 expressing eGFP (enhanced green fluorescent protein) (Apoe-/- ChemR23-knockout/knockin mice). These mice are fed a Western Diet (WD) for 4 or 12 weeks and analysed for ATMs and their phenotype via FACS. Using two Cre-lox mouse models with a cell-specific knockout of ChemR23 either on adipocytes or myeloid cells with an Apoe-/- deficient background will enable us to examine the impact of ChemR23 on those cells and to better understand the adipocyte-macrophage interaction in the absence of the receptor.

We found that the systemic knockout of ChemR23 decreased the number of macrophages in various adipose tissues including the periaortic adipose tissue (PVAT) after 4 weeks of WD (ChemR23eGFP n=6; Apoe-/- n=4, p < 0.05, CI = 0.1360 to 7.481). Furthermore, the number of classically activated M1 macrophages increased in adipose tissues of mice lacking the ChemR23 receptor fed a WD for 4 weeks (ChemR23eGFP n=8; Apoe-/- n=4, p > 0.05, CI = -872.6 to 1032).

Based on previous data, we hypothesize that the loss of ChemR23 expression has an adverse effect on the phenotypic switching of ATMs in PVAT in hyperlipidaemic mice during atherosclerosis. Further investigations are planned for unravelling the transcriptome of ATMs using scRNA sequencing and employing mouse models with cell a specific knockout of ChemR23 to establish a primary macrophage and adipocyte cell culture.