Identification of Macrophage Genotype and Key Biological Pathways in Circulating Angiogenic Cell Transcriptome

Bert R Everaert; Steven J Van Laere; Robrecht Lembrechts; Vicky Y Hoymans; Jean-Pierre Timmermans; Christiaan J Vrints

doi:10.1155/2019/9545261

Identification of Macrophage Genotype and Key Biological Pathways in Circulating Angiogenic Cell Transcriptome

Stem Cells Int. 2019 May 2:2019:9545261. doi: 10.1155/2019/9545261. eCollection 2019.

Authors

Bert R Everaert^{1

2}, Steven J Van Laere³, Robrecht Lembrechts¹, Vicky Y Hoymans², Jean-Pierre Timmermans¹, Christiaan J Vrints²

Affiliations

¹ Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.
² Laboratory of Cellular and Molecular Cardiology, Antwerp University Hospital, Edegem, Belgium.
³ Translational Cancer Research Unit, Oncology Center, St-Augustinus Hospital, Wilrijk, Belgium.

Abstract

Background: Circulating angiogenic cells (CAC) have been identified as important regulators of vascular biology. However, there is still considerable debate about the genotype and function of CAC.

Methods and results: Data from publicly available gene expression data sets were used to analyse the transcriptome of in vitro cultured CAC (CAC_iv). Genes and pathways of interest were further evaluated using qPCR comparing CAC_iv versus CD14⁺ monocytic cells. The CAC_iv transcriptome strongly related to tissue macrophages, and more specifically to regulatory M2c macrophages. The cytokine expression profile of CAC_iv was predominantly immune modulatory and resembled the cytokine expression of tumor-associated macrophages (TAM). Pathway analysis revealed previously unrecognized biological processes in CAC_iv, such as riboflavin metabolism and liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR)/retinoid X receptor (RXR) pathways. Analysis of endothelial-specific genes did not show evidence for endothelial transdifferentiation.

Conclusions: CAC_iv are genotypically similar to regulatory M2c macrophages and lack signs of endothelial differentiation.