CORRELATION OF MECHANICAL BEHAVIOR AND MMP-1 PRESENCE IN HUMAN ATHEROSCLEROTIC PLAQUE

Abstract

Regions of matrix metalloproteinase (MMP) activity potentially increase the susceptibility of the atherosclerotic lesion to complications associated with plaque rupture. Assessing the risk posed by this mechanism requires investigating the stress-strain environment associated with matrix metalloproteinase production in heterogeneous plaque. To this end, an experimental-computational technique was developed to perform mechanical analysis of physiologically loaded, diseased human aorta in vitro and to investigate relationships between vascular mechanics, histology, and histochemistry. Mechanical data and specimen histology were coupled through a heterogeneous finite element model, and tissue constituent material properties were determined by an optimization method. The cross-sectional distribution of MMP-1 was quantified using immunohistochemical techniques. Results show stresses and strains are strongly influenced by lesion structure and composition, and MMP-1 presence is correlated with histology and lesion mechanics. Interactions between lipid presence, mechanical stimuli, and extracellular matrix metabolism-catabolism likely affect arterial plaque remodeling, progression, and the risk of disruption and clinical symptoms.