SUMMARY

Cardiovascular disease (CVD) is the leading cause of death in the United States. One of the primary causes of CVD is atherosclerosis; rupture of atherosclerotic plaque is responsible for most instances of myocardial infarction and stroke. Plaques that are vulnerable to rupture have several common characteristics. They tend to be large eccentric plaques, with considerable positive remodeling, large lipid pools, thin fibrous caps, and significant inflammatory infiltration. Finite element studies have shown that mechanical stress is increased in the shoulder and fibrous cap region, where plaques most often rupture. Furthermore, inflammatory markers such as macrophages and MMPs have been found to localize in these regions. However, attempts to spatially correlate inflammation and mechanical stress are few, and have been limited by the difficulty of quantifying the distribution of inflammatory markers. In addition, previous finite element models have done little to capture the heterogeneous nature of plaque tissue, and so are potentially inaccurate. A better understanding of the collocation of stress and inflammation in atherosclerosis will yield insight into the mechanisms of plaque rupture. The proposed research will develop a finite element model that accounts for the spatial heterogeneity of plaque. In addition, quantitative methods for determining inflammatory cell spatial distributions will be developed. These methods will then be used to investigate the spatial correlation of mechanical stress with important markers of inflammation.