Regions of Low Endothelial Shear Stress Colocalize With Positive Vascular Remodeling and Atherosclerotic Plaque Disruption

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Background— Local hemodynamic factors, particularly low endothelial shear stress (ESS), play a role in the focal formation of atherosclerosis. We used in vivo MRI to investigate the role of the magnitude of ESS on vascular remodeling, plaque burden, and disruption using a rabbit model of controlled atherothrombosis. Methods and Results— Atherosclerosis was induced in New Zealand white rabbits by cholesterol diet and endothelial denudation. MRI was performed before (pretrigger) and after (posttrigger) inducing plaque disruption with Russell viper venom and histamine. Of the 134 vascular segments studied, 28 contained thrombus (disrupted) and 106 did not (nondisrupted). Disrupted plaques were histologically characterized by a thin, inflamed fibrous cap, a dense lipid core, and mural thrombus. Pretriggered MRI revealed that disrupted plaques clustered at regions with low mean ESS (11.55±5.3 versus 20.9±9.74 dynes/cm 2 ; P <0.001) and low peak ESS (21.5±11.2 versus 49.2±21.5 dynes/cm 2 ; P <0.001) compared with nondisrupted plaques. The peak ESS negatively correlated with the plaque area ( r =−0.56, P <0.001) and remodeling ratio ( r =−0.4, P =0.008). There was also a negative correlation between the mean ESS and the remodeling ratio ( r =−0.55, P <0.001). Both the peak ESS and the mean ESS did not correlate with the % stenosis; there was a weak but statistically significant correlation with the % cross-sectional narrowing ( r =0.3, P =0.002 and r =0.2, P =0.04, respectively). Receiver operating characteristic analysis showed that both mean (AUC=0.78; 95% CI, 0.69–0.87) and peak ESS (AUC=0.85; 95% CI, 0.78–0.93) identified disrupted plaques. Conclusions— We demonstrated that low ESS is associated with plaque burden, positive vascular remodeling, and plaque disruption in a rabbit model. Assessment of ESS by noninvasive MRI might be useful for assessing atherosclerotic risk.