Date of Award

2012

Document Type

Campus Access Dissertation

Department

Biomedical Engineering

First Advisor

SUSAN M LESSNER

Abstract

Atherosclerotic plaque rupture is a major cause of myocardial infarction and stroke. The adhesive strength of the bond between the plaque and the vascular wall, measured as local energy release rate, G, was used for quantitative plaque stability estimation in mouse models. Towards the long-range goal of developing methods to predict incipient plaque failure in human atherosclerosis, we also applied peeling tests on human Left Anterior Descending (LAD) coronary arteries to investigate interlaminar adhesive strength of vessels.

Our results indicate a significant effect of genotype on measured G values for plaques in apoE knockout (KO) and apoE MMP12 double knockout (DKO) mice. Histological studies confirmed that the plaques delaminated at the interface between the plaque and the underlying internal elastic lamina (IEL) in both strains of mice. We found a positive linear correlation between local collagen content of lesions and G values in both strains of mice. The average collagen content for plaques in apoE KO and apoE MMP12 DKO mice was not significantly different. Immunohistochemical staining showed that macrophage content of aortic plaques is neither significantly correlated with G values nor significantly different between these two strains of mice. Overall, our results suggest that plaques adhere more strongly to the underlying IEL in apoE KO mice than in apoE MMP12 DKO mice. Our results indicate that the interlaminar adhesive strength of human LADs falls within the same order of magnitude as that of mouse samples.

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