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Transl Res. 2022 Feb;240:33-49. doi: 10.1016/j.trsl.2021.08.007. Epub 2021 Aug 31.

Predictive mouse model reflects distinct stages of human atheroma in a single carotid artery.

Translational research : the journal of laboratory and clinical medicine

Joyce Ms Chan, Sung-Jin Park, Michael Ng, Way Cherng Chen, Joanne Garnell, Kishore Bhakoo

Affiliations

  1. Translational Cardiovascular Imaging Group, Institute of Bioengineering and Bioimaging (IBB), Agency for Science, Technology and Research (A*STAR), Singapore. Electronic address: [email protected].
  2. Translational Cardiovascular Imaging Group, Institute of Bioengineering and Bioimaging (IBB), Agency for Science, Technology and Research (A*STAR), Singapore.
  3. Bruker Singapore Pte. Ltd., Singapore.
  4. Translational Imaging Laboratory, Institute of Bioengineering and Bioimaging (IBB), Agency for Science, Technology and Research (A*STAR), Singapore.

PMID: 34478893 DOI: 10.1016/j.trsl.2021.08.007

Abstract

Identification of patients with high-risk asymptomatic atherosclerotic plaques remains an elusive but essential step in preventing stroke. However, there is a lack of animal model that provides a reproducible method to predict where, when and what types of plaque formation, which fulfils the American Heart Association (AHA) histological classification of human plaques. We have developed a predictive mouse model that reflects different stages of human plaques in a single carotid artery by means of shear-stress modifying cuff. Validated with over 30000 histological sections, the model generates a specific pattern of plaques with different risk levels along the same artery depending on their position relative to the cuff. The further upstream of the cuff-implanted artery, the lower the magnitude of shear stress, the more unstable the plaques of higher grade according to AHA classification; with characteristics including greater degree of vascular remodeling, plaque size, plaque vulnerability and inflammation, resulting in higher risk plaques. By weeks 20 and 30, this model achieved 80% and near 100% accuracy respectively, in predicting precisely where, when and what stages/AHA types of plaques develop along the same carotid artery. This model can generate clinically-relevant plaques with varying phenotypes fulfilling AHA classification and risk levels, in specific locations of the single artery with near 100% accuracy of prediction. The model offers a promising tool for development of diagnostic tools to target high-risk plaques, increasing accuracy in predicting which individual patients may require surgical intervention to prevent stroke, paving the way for personalized management of carotid atherosclerotic disease.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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