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Dilated microvessel with endothelial cell proliferation involves intraplaque hemorrhage in unstable carotid plaque

Daina Kashiwazaki¹, Shusuke Yamamoto², Naoki Akioka²

¹Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. dkashiwa@med.u-toyama.ac.jp.

Acta Neurochirurgica

|September 30, 2020

Insights

Dilated microvessels in carotid plaques, particularly those with intraplaque hemorrhage, are linked to increased endothelial cell proliferation and a higher risk of recurrent ischemic events. This highlights their role in plaque vulnerability and clinical outcomes.

Area of Science:

Vascular Biology
Cardiovascular Research
Pathology

Background:

Vulnerable plaques in carotid arteries pose a significant risk for ischemic events.
Intraplaque microvessels and endothelial cell (EC) proliferation are key factors in plaque instability.
Understanding EC proliferation in microvessels is crucial for assessing plaque vulnerability.

Purpose of the Study:

To characterize endothelial cell (EC) proliferation in intraplaque microvessels of vulnerable carotid plaques.
To investigate the impact of these microvascular characteristics on clinical outcomes, including ischemic events.

Main Methods:

Carotid endarterectomy specimens from 76 patients were analyzed.
Patients were grouped by symptomatic status: asymptomatic, symptomatic without recurrence, and symptomatic with recurrence.
Immunohistochemistry quantified microvessel density (CD31+), EC proliferation (Ki67+, CD105+), and microvessel diameter.

Main Results:

Plaques with intraplaque hemorrhage (IPH) showed significantly larger microvessels (56.4 ± 10.0 μm) and higher EC proliferation (19.5 ± 5.9% Ki67+/CD31+) compared to lipid-rich and fibrous plaques.
Dilated microvessels (>40 μm) were most prevalent in IPH plaques (9.6%).
Larger microvessel diameters and higher EC proliferation correlated with symptomatic status and recurrent ischemic events (p < 0.01).

Conclusions:

Dilated intraplaque microvessels with proliferative endothelial cells are prominent in vulnerable plaques, especially those with IPH.
These microvascular features are associated with the pathogenesis of IPH and predict clinical onset and recurrence of ischemic events.
Targeting these microvessels may offer therapeutic potential for managing vulnerable carotid plaques.

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Abstract

Background:

The purpose of the present study was to clarify the characteristics of endothelial cell (EC) proliferation in intraplaque microvessels in vulnerable plaques and impact on clinical results.

Methods:

The present study included 76 patients who underwent carotid endarterectomy. Patients were classified into three groups based on their symptoms: asymptomatic, symptomatic without recurrent ischemic event, and symptomatic with recurrent ischemic event. MR plaque imaging was performed and surgical specimens underwent immunohistochemical analysis. The number of CD31⁺ microvessels, and Ki67⁺ and CD105⁺ ECs in the carotid plaques was quantified, as measurements of maximum CD31⁺ microvessel diameter.

Results:

MR plaque imaging yielded 41 subjects (54.0%) diagnosed with plaque with intraplaque hemorrhage (IPH), 14 subjects (18.4%) diagnosed with fibrous plaques, and 21 (27.6%) subjects diagnosed with lipid-rich plaques. The average largest diameter of microvessel in fibrous plaques, lipid-rich plaques, and plaque with IPH was 12.7 ± 4.1 μm, 31.3 ± 9.3 μm, and 56.4 ± 10.0 μm, respectively (p < 0.01). Dilated microvessels (>40 μm) were observed in 9.6% of plaques with IPH but only in 2.8% of lipid-rich plaques and 0% of fibrous plaques (p < 0.01). Ki67⁺/CD31⁺ ECs were identified in 2.8 ± 1.2% of fibrous plaques, 9.6 ± 6.9% of lipid-rich plaques, and in 19.5 ± 5.9% of plaques with IPH (p < 0.01). The average largest diameter of microvessels in the asymptomatic group was 17.1 ± 8.7 μm, 32.3 ± 10.8 μm in the symptomatic without recurrence group, and 55.2 ± 13.2 μm in the symptomatic with recurrence group (p < 0.01).

Conclusion:

Dilated microvessels with proliferative ECs may play a key role in IPH pathogenesis. Furthermore, dilated microvessels are likely related to clinical onset and the recurrence of ischemic events. The purpose of the present study was to clarify the characteristics of EC proliferation in intraplaque microvessels in vulnerable plaques and their impact on clinical results, focusing on dilated intraplaque microvessels.

Keywords:

Carotid stenosis Dilated microvessel Intraplaque hemorrhage Ischemic stroke

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