Abstract
Objective: Circulating angiogenic cells (CACs) have been identified as important regulators of vascular biology. However, there is still considerable debate about the phenotype and function of CACs. Methods and results: DNA microarray transcriptome analysis was used to study the CAC phenotype and investigate the key biological pathways in CAC biology. We determined a CAC-specific gene signature, which revealed the close relationship between CACs and members of the macrophage lineage, such as tumor-associated macrophages (TAMs), dendritic cells (DCs), osteoclasts and atherosclerotic plaque-remodeling macrophages. We identified CCL2, CCL17, CCL18 and CCL22 as a chemokinetic fingerprint for CACs and indicated cholesterol transporter pathways (LXR/RXR, FXR/RXR) and riboflavin metabolism as highly important biological pathways in the CAC transcriptome. These findings, together with upregulation of the chemokine receptor CCR7, suggest the involvement of CACs in reverse plaque remodeling. Conclusions: CACs are phenotypically similar to regulatory M2 macrophages and lack signs of endothelial differentiation. However, the expression profile of CACs prompted us to suggest new mechanisms by which these cells could engage in cardiovascular pathophysiology, such as immunomodulation, tissue remodeling, enhancement of cholesterol efflux and vasculoprotection. These findings expand the current knowledge on CAC biology and suggest new indications for CAC therapy in future clinical trials.
Published Version
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