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  • Molecular Signatures of Carotid Plaques

    Final Number:

    Georgios A Zenonos MD; Ellen Caparosa MD; Andrew J Sedgewick PhD; Ana-Carolina Igami Nakassa MD; William Lariviere PhD; Yin Zao; Diane Carisle PhD; Lucia Stefaneanu; Brian T. Jankowitz MD; Paul A. Gardner MD; Yue-Fang Chang PhD; William Laframboise; Panayiotis Benos; Robert Max Friedlander MD

    Study Design:
    Laboratory Investigation

    Subject Category:
    Basic Science

    Meeting: AANS/CNS Cerebrovascular Section 2018 Annual Meeting

    Introduction: Our ability to predict which atherosclerotic plaques are at higher risk to become symptomatic is limited, resulting in numerous unnecessary interventions. A better understanding of the molecular signatures associated with rupture-prone plaques, and the development of peripheral biomarkers could help guide management

    Methods: Thirty-eight carotid plaques (26 symptomatic, 12 asymptomatic), obtained from carotid endarterectomies at our institution, were dissected into pre-bifurcation, bifurcation, and post-bifurcation segments. All were used for protein expression. In addition, 9 symptomatic, and 9 asymptomatic plaques were used to identify mRNA:miRNA interactions in the post-bifurcation segments. Furthermore, peripheral blood from 9 patients with symptomatic plaques, and 9 patients with asymptomatic plaques, as well as 3 normal controls were used to evaluate peripheral miRNA expression.

    Results: Protein expression profiles revealed increased levels of IL-1ß , IL-6, IL-8, and cleaved caspace-3 in symptomatic compared to asymptomatic plaques, and in the distal, compared to the proximal plaque segments (post-bifurcation> bifurcation> pre-bifurcation). Further analysis of the post-bifurcation segments revealed three high-confidence miRNA:mRNA pair interactions (negatively correlated) that were differentially expressed between symptomatic and asymptomatic plaques: hsa-miR-214/APOD, hsa-miR-484/DACH1, hsa-miR-942/GPR56 (p < 0.001, correlation q < 0.05). Evaluation of peripheral blood miRNA expression revealed 7 miRNAs to be differentially expressed between symptomatic, and asymptomatic plaques, and 13 miRNAs to be differentially expressed between symptomatic plaques and controls.

    Conclusions: The current study identifies a number of novel potential biomarkers for carotid plaque vulnerability. Prospective evaluation of these markers in a large number of patients with carotid stenosis is warranted to establish their clinical applicability

    Patient Care: The current study identifies novel biomarkers of carotid plaque vulnerability, which could help risk stratify patients with carotid stenosis, and allow better patient selection for carotid revascularization procedures

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) discuss the importance of biomarkers in the risk stratification of carotid stenosis, 2) describe some of the most important novel biomarkers presented in this study


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