Coronary arterial dynamics and atherogenesis

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DESCRIPTION (provided by applicant): Although risk factors for atherosclerosis (AS) are systemic in nature, certain arteries (e.g. coronary arteries) are more susceptible to AS than others. The coronary arteries experience the added mechanical forces of cyclic flexing, stretching and twisting due to their tethering to a beating heart suggesting that both shear and mural stress are contributors to AS. Hypothesis: Local variations in shear and mural stress associated with dynamic motion of arterial segments influence the distribution of early markers of atherogenesis. Specific Aims: (1) Determine experimentally the extent and spatial distribution of early markers (i.e. endothelial injury, lipid accumulation, and inflammatory activation) of atherogenesis in intact arterial segments exposed to physiologically realistic ex vivo perfusion conditions including cyclic flexure, stretch and twist; (2) Estimate the shear and mural stress distributions specifically for each experimentally perfused arterial segment using computational fluid dynamics and computational solid stress analyses, respectively; (3) Determine the correlative relationships between the shear and mural stress distributions estimated computationally and the spatial variation of atherogenic endpoints determined experimentally.