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

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.

Automated summary

This study developed a predictive mouse model that can accurately predict the formation location, time, and type of plaques in the carotid artery, allowing for identification of high-risk asymptomatic atherosclerotic patients.