| It has been hypothesized that adverse hemodynamic conditions, such as flow recirculation and low wall shear stress, play a large role in the localization of cardiovascular disease. The vascular endothelium, a single layer of cells comprising the innermost layer of every blood vessel, has been shown to sense and respond to biomechanical forces such as shear stress. Therefore, it is believed that the local flow environment is able to regulate endothelial cell function and dysfunction, thus contributing to the initiation, progression, or prevention of disease.; These hypotheses have necessitated the quantification of in vivo hemodynamic conditions. In this work, a combined magnetic resonance imaging and computational fluid dynamics approach was incorporated to investigate hemodynamic conditions under resting and exercise conditions in the human abdominal aorta and pulmonary arteries. These techniques were also applied to studying the pulmonary arteries of patients with Pulmonary Arterial Hypertension (PAH), a rare and chronic disease. It was found that wall shear stress was lower, and oscillations in shear stress were higher, in regions of the vasculature known to be more prone to atherosclerosis as well as in the pulmonary arteries of PAH patients versus normal subjects, thus supporting the hypothesis of a correlation between adverse hemodynamic conditions and disease localization. Under exercise conditions, wall shear stress was significantly increased and oscillations in wall shear were significantly decreased in these areas, demonstrating the local biomechanical benefits of exercise.; The results obtained from these computational simulations were used to guide in vitro shear stress experiments on human endothelial cells. Specifically, the effects of brief time courses of increased shear stress on human aortic endothelial cell gene expression were analyzed to address the biomechanical mechanism by which short bouts of exercise have lasting effects on endothelial biology. In addition, the effects of PAH shear stress levels on pulmonary artery endothelial cell gene expression were studied to reveal mechanisms by which altered shear stress may play a role in endothelial dysfunction and disease progression. These in vitro experiments provided a correlation between the shear stresses that were quantified via computational simulations and their biological impact. |
