Involvement of circulating endothelial progenitor cells in carotid plaque growth and vulnerability

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  • 1 Departments of Neurosurgery and
  • | 2 Radiology, Graduate School of Medicine and Pharmacological Sciences, University of Toyama; and
  • | 3 Department of Neurology, Toyama University Hospital, Toyama, Japan
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OBJECTIVE

The roles of endothelial progenitor cells (EPCs) in the development of carotid plaque are still obscure. This study aimed to clarify this by assessing the histological findings of specimens obtained from carotid endarterectomy.

METHODS

This study included 34 patients who underwent carotid endarterectomy. MR imaging was performed to semiquantitatively analyze the components of the carotid plaques in all patients. The surgical specimens were subjected to immunohistochemistry. The distributions of the CD34-, CD133-, VEGF-2R–positive cells in the carotid plaques were precisely analyzed, and their number was quantified. Simultaneously, the CD34-positive microvessels were localized.

RESULTS

The plaque component was judged as lipid-rich plaque in 19 patients, intraplaque hemorrhage (IPH) in 11 patients, and fibrous plaque in 4 patients. The CD34-positive microvessels were densely distributed in the plaque shoulder and interface-to-media regions. The CD34-, CD133-, and VEGF-2R–positive cells were mainly localized around the CD34-positive microvessels. The number of CD34-positive microvessels significantly correlated with the number of CD34-, CD133-, and VEGF-2R–positive cells (R = 0.308, p = 0.009; R = 0.324, p = 0.006; and R = 0.296, p = 0.013, respectively). Vulnerable plaques (lipid-rich and IPH) had significantly higher numbers of the CD34-positive microvessels (p = 0.007) and CD34-, CD133-, and VEGF-2R–positive cells than fibrous plaques (p = 0.031, p = 0.013, and p = 0.002).

CONCLUSIONS

These findings strongly suggest that neovascularization in the plaque shoulder and interface-to-media regions may play a key role in delivering EPCs from the peripheral blood to the carotid plaque, promoting the growth of carotid plaque. Furthermore, the invaded EPCs, especially the CD133-positive immature EPCs, may be related to plaque vulnerability.

ABBREVIATIONS

EPC = endothelial progenitor cell; FOV = field of view; IPH = intraplaque hemorrhage; TOF = time of flight.

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