Surface expression of CXCR4 on circulating CD133progenitor 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.

Figure 1

Example of lesion type IV-V in the right internal carotid artery. The necrotic core (←) shows low-signal intensity (SI) on both T1w and TOF images, but low SI to iso-SI on PDW and T2w images. Original magnification × 25.

Figure 2

Example of lesion type VIII in the right internal carotid artery. Lesion type VIII (←) in the right internal carotid artery. MR images show iso- to slightly high-SI. Original magnification × 25.

Figure 3

Number of CD133⁺ progenitor cells. Boxplot demonstrating the number of CD133⁺ progenitor cells (/μl) in subjects with stable plaques and subjects with unstable plaques. The top of the box represents the 75th percentile, the bottom of the box represents the 25th percentile, the center horizontal line represents the 50th percentile. The whiskers represent the highest and lowest values that are not outliers or extreme values. Outliers (between 1.5 and 3 times the interquartile range) are represented by circles and extreme values (more than 3 times the interquartile range) by asterisks.

Figure 4

Number of VEGFR2⁺CD34⁺ progenitor cells. Boxplot demonstrating the number of VEGFR2⁺CD34⁺ progenitor cells (/μl) in subjects with stable plaques and subjects with unstable plaques. The top of the box represents the 75th percentile, the bottom of the box represents the 25th percentile, the center horizontal line represents the 50th percentile. The whiskers represent the highest and lowest values that are not outliers or extreme values. Outliers (between 1.5 and 3 times the interquartile range) are represented by circles and extreme values (more than 3 times the interquartile range) by asterisks.

Figure 5

Surface expression of CXCR4 on CD133⁺ progenitor cells. Boxplot demonstrating the surface expression of CXCR4 on CD133⁺ progenitor cells in subjects with stable plaques and subjects with unstable plaques. The top of the box represents the 75th percentile, the bottom of the box represents the 25th percentile, the center horizontal line represents the 50th percentile. The whiskers represent the highest and lowest values.