J Korean Neurosurg Soc.  2020 Mar;63(2):178-187. 10.3340/jkns.2019.0077.

Vasa Vasorum Densities in Human Carotid Atherosclerosis Is Associated with Plaque Development and Vulnerability

• Joo SP
• Lee SW
• Cho YH
• Kim YS
• Seo BR
• Kim HS
• Kim TS

• KMID: 2501704
• DOI: http://doi.org/10.3340/jkns.2019.0077

Abstract

Objective
: The extensive vasa vasorum network functions as a conduit for the entry of inflammatory cells or factors that promote the progression of angiogenesis and plaque formation. Therefore, we investigated the correlation between the carotid vasa vasorum activities and carotid plaque vulnerability using indocyanine green video angiography (ICG-VA) during carotid endarterectomy (CEA).
Methods
: Sixty-nine patients who underwent CEA were enrolled prospectively from September 2015 to December 2017. During CEA, a bolus of ICG was injected intravenously before and after resecting the atheroma. Additionally, we performed immunohistochemistry using CD68 (a surface marker of macrophages), CD117 (a surface marker of mast cells), and CD4 and CD8 (surface markers of T-cells) antibodies to analyze the resected plaque specimens.
Results
: The density of active vasa vasorum was observed in all patients using ICG-VA. The vasa vasorum externa (VVE) and interna (VVI) were seen in 11 (16%) and 57 patients (82.6%), respectively. Macroscopically, the VVE-type patterns were strongly associated with preoperative angiographic instability (81.8%, p=0.005) and carotid plaque vulnerability (90.9%, p=0.017). In contrast, the VVI-type patterns were weakly associated with angiographic instability (31.6%) and plaque vulnerability (49.1%). CD68-stained macrophages and CD117-stained mast cells were observed more frequently in unstable plaques than in stable plaques (p<0.0001, p=0.002, respectively).
Conclusion
: The early appearance of VVE, along with the presence of many microvessel channels that provided nutrients to the developing and expanding atheroma during ICG-VA, was strongly associated with unstable carotid plaques. The degree of infiltration of macrophages and mast cells is possibly related to the formation of unstable plaques.

Keyword

Atherosclerosis; Plaque, Atherosclerotic; Endarterectomy, Carotid; Indocyanine green; Vasa vasorum

Figure

• 

  Fig. 1. Illustration showing the three vasa vasorum patterns based on surface anatomy or indocyanine green-video angiography (ICG-VA) appearance. Modified according to Schoenenberger and Mueller [33]. I : intima, M : media, A : adventia.

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  Fig. 2. Representative case of vasa vasorum externa. A 67-year-old woman presented with repeated episodes of left-sided motor weakness and dysarthria. A : Diffusion-weighted magnetic resonance image showing an acute infarction on the insular cortex. B : Carotid artery angiogram showing the unstable plaque (arrows). C : Indocyanine green video angiography image demonstrating an early depiction of the vasa vasorum externa (arrows). D : Intraoperative findings indicating unstable plaque—a necrotic core within the atheroma.

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  Fig. 3. Representative case of vasa vasorum interna (VVI). A 65-year-old man presented with dysarthria and left hemiparesis grade II/IV and NIHSS 3. A : Diffusion-weighted magnetic resonance image showing a multifocal acute infarction on the right hemisphere. B : Carotid artery angiogram showing a carotid stenosis with a stable plaque (arrowheads). C : ICG-VA image demonstrating a delayed depiction of the VVI with abundant vascular channels (arrowheads). Postoperative ICG-VA image showing disappearance of the vasa vasorum vascular networks (bottom). D: Intraoperative findings indicating stable plaque—a smooth luminal surface (circle). NIHSS : National Institutes of Health Stroke Scale, ICG-VA : indocyanine green video angiography.

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  Fig. 4. Representative case of vasa vasorum venosum (VVV). A 64-year-man presented with a recurrent a transient ischemic attack on the left side with a history of smoking. A : Carotid artery angiogram showing carotid stenosis (60%, the North American Symptomatic Carotid Endarterectomy Trial). B : Indocyanine green-video angiography image demonstrating delayed depiction of the VVV (arrowheads) along with the carotid bulb. C : Intraoperative findings indicating stable plaque—smooth outer and inner surfaces.

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  Fig. 5. Depiction of inflammatory cell (macrophages and mast cells) activities in a resected plaque by immunohistochemistry studies. CD68-stained macrophages and CD117-stained mast cells were more frequently observed in unstable plaque, than in stable plaque (p<0.0002, p<0.0001, respectively). However, no significant differences in the frequencies of occurrence of CD4 or CD8 T-cells were observed between stable and unstable plaques.

Reference

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