Surface expression of CXCR4 on circulating CD133+progenitor cells is associated with plaque instability in subjects with carotid artery stenosis

Abstract

Background

Circulating progenitor cells (PCs) are considered to contribute to the remodeling of atherosclerotic plaques. Their surface receptor CXCR4 plays an important role in the recruitment of PCs to their target. This study compares the mobilization of PCs and their functional characteristics in asymptomatic subjects with stable and with unstable carotid plaques. This could provide insight into plaque remodeling and help to develop biomarkers for plaque stability.

Methods

In 31 subjects with asymptomatic carotid artery stenosis we analyzed the number of CD133 ⁺PCs, VEGFR2 ⁺CD34 ⁺PCs and the surface expression of CXCR4 on CD133 ⁺PCs by flow cytometry. Subjects underwent bilateral carotid MRI in a 1.5-T scanner in order to allow the categorization of plaques, following the modified criteria of the American Heart Association.

Results

The number of CD133 ⁺PCs and VEGFR2 ⁺CD34 ⁺PCs showed no significant difference between subjects with stable and unstable carotid plaques. The expression of CXCR4 on CD133 ⁺PCs was higher in subjects with unstable plaques than in subjects with stable plaques (p = 0.009).

Conclusions

This study demonstrates an association between functional characteristics of circulating CD133 ⁺PCs and plaque stability in subjects with asymptomatic carotid artery stenosis. The higher expression of CXCR4 on CD133 ⁺PCs suggests a difference in the recruitment of PCs to the injured tissue in subjects with unstable plaques and subjects with stable plaques. As surface expression of CXCR4 on CD133 ⁺PCs differs in subjects with unstable and with stable plaques, CXCR4 is a promising candidate for a serological biomarker for plaque stability.