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. 2020 Mar 13;21(6):1980.
doi: 10.3390/ijms21061980.

Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings

Atsushi Ogata  1 , Tomihiro Wakamiya  1 , Masashi Nishihara  2 , Tatsuya Tanaka  1   3 , Taichiro Mizokami  1   4 , Jun Masuoka  1 , Nobuaki Momozaki  3 , Shuji Sakata  4 , Hiroyuki Irie  2 , Tatsuya Abe  1
Affiliations

Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings

Atsushi Ogata et al. Int J Mol Sci. .

Abstract

(1) Background: Pericytes are involved in intraplaque neovascularization of advanced and complicated atherosclerotic lesions. However, the role of pericytes in human carotid plaques is unclear. An unstable carotid plaque that shows high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) is often a cause of ischemic stroke. The aim of the present study is to examine the relationship between the pericytes in intraplaque neovessels and MRA findings. (2) Methods: A total of 46 patients with 49 carotid artery stenoses who underwent carotid endarterectomy at our hospitals were enrolled. The patients with carotid plaques that were histopathologically evaluated were retrospectively analyzed. Intraplaque hemorrhage was evaluated using glycophorin A staining, and intraplaque neovessels were evaluated using CD34 (Cluster of differentiation) stain as an endothelial cell marker or NG2 (Neuron-glial antigen 2) and CD146 stains as pericyte markers. Additionally, the relationships between the TOF-MRA findings and the carotid plaque pathologies were evaluated. (3) Results: Of the 49 stenoses, 28 had high-intensity signals (TOF-HIS group) and 21 had iso-intensity signals (TOF-IIS group) on TOF-MRA. The density of the CD34-positive neovessels was equivalent in both groups. However, the NG2- and CD146-positive neovessels had significantly higher densities in the TOF-HIS group than in the TOF-IIS group. (4) Conclusion: The presence of a high-intensity signal on TOF-MRA in carotid plaques was associated with intraplaque hemorrhage and few pericytes in intraplaque neovessels. These findings may contribute to the development of new therapeutic strategies focusing on pericytes.

Keywords: carotid artery; carotid stenosis; magnetic resonance imaging; pericyte.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Relationships between time-of-flight magnetic resonance angiography (TOF-MRA) signal intensity and (A) glycophorin A-positive area and (B) CD68-positive area. The glycophorin A and CD68-positive areas are significantly larger in the TOF-HIS group (high-intensity signal plaques) than in the TOF-IIS (iso-intensity signal plaques) group. p-values are based on the Student’s t-test.
Figure 2
Figure 2
Relationship between TOF-MRA signal intensity and the number of neovessels. The difference in the number of CD34-positive neovessels according to TOF-MRA signal intensity is not significant. The p-value is based on the Student’s t-test (A). The numbers of NG2-positive (B) and CD146-positive (C) neovessels are significantly lower in the TOF-HIS group than in the TOF-IIS group. P-values are based on the Student’s t-test. The correlation between the numbers of NG2 and of CD146-positive neovessels is significant. Spearman’s rank correlation test was used to assess correlations (D).
Figure 3
Figure 3
Representative cases of the TOF-HIS group (A) and the TOF-IIS group (B). Carotid plaques with high intensity (arrowhead) and iso intensity (arrow) signals on TOF-MRA. The photomicrographs of immunohistochemistry show many glycophorin A and CD68-positive cells in the TOF-HIS group. In both groups, CD34-positive neovessels are equally distributed. NG2 and CD146-positive neovessels are densely distributed in the TOF-IIS group. Square outlines indicate plaque shoulder lesions.
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