Ph.D. Proposal Presentation by Yu Shin Kim
Friday, March 18, 2005

(Dr. Raymond Vito, Chair)

"Correlation between MMP-2 and -9 Levels and Local Stresses in Arteries Using a Heterogeneous Mechanical Model"

Abstract

The mechanical environment influences vascular smooth muscle cell (VSMC) functions related to the remodeling of blood vessels. However, the relationships are not appropriately addressed by most mechanical models of arteries assuming homogeneity. Accounting for the effects of heterogeneity may be important to our understanding of VSMC functions. In this study, a mechanical model of an arterial wall, including microstructural heterogeneity, will be developed and used to determine the correlation between local mechanics and VSMC activities. It is hypothesized that the distribution of mechanical stress and strain in the extracellular matrix (ECM) influences the localization of expression and activation of matrix metalloproteinase (MMP)-2 and -9 by VSMCs in situ .

A multi-layered mechanical model of an artery will be developed based on the measurements of two major ECM components, elastin and collagen. The heterogeneous model will account for nonlinear elasticity and residual stress and strain with varying mechanical properties through the arterial wall. The amounts of elastin and collagen in each layer will be quantified using histology and microscopy. The proposed research will use an ex vivo organ culture system to incubate arteries under controlled mechanical environment. After organ culture, the localization of MMP-2 and -9 will be assessed using immunohistochemistry and in situ zymography and correlated to local mechanical stresses predicted using the heterogeneous model. The mechanical and structural continuity between VSMCs and ECM will be investigated by quantifying distributions of VSMC nuclear morphology three-dimensionally reconstructed using confocal microscopy.

The proposed research will show how accounting for structural heterogeneity affects the utility of mechanical models for studies of the collocation of local mechanics and cellular activities. The methodology developed in this research could provide a means to evaluate and influence the functionality of tissue-engineered vascular grafts.