Mechanical Role of Elastin in Arterial Development and Disease Progression

Abdominal and thoracic aortic aneurysms are focal dilatations of the aorta that typically assume a fusiform shape and often progress to rupture, which is increasingly responsible for mortality and morbidity in our aging population. Although aneurysmal pathogenesis remains unclear, loss of medial elastin, the primary component of elastic fibers in arteries, is one of the fundamental histopathologic features of aneurysmal degeneration of the thoracic and abdominal aorta. The present work of thesis was carried out at the Continuum Biomechanics Laboratory of Texas A&M University, under the supervision of Prof. Jay D. Humphrey. The main goal of this thesis is to study the role of collagen and elastin, with a particular focus on the latter, in determining the passive biaxial mechanical behavior of large arteries. In order to quantify the response of single arterial wall constituents under biaxial loading, a new, structurally-motivated “four fiber family” nonlinear constitutive relation was fitted to experimental data via nonlinear regression. Confidence intervals for material and structural parameters were determined using the nonparametric bootstrap method, which allows determination of the precision of the parameter estimation procedure with the least assumptions. This analysis was first applied to describe the mechanical behavior of both human abdominal aorta (AA) and abdominal aortic aneurysm (AAA). Results show that the model is able to capture the mechanical behavior of the arterial tissue in both groups and the estimated parameters provide structural information about modifications of the arterial wall with aging and aneurysmal disease. Motivated by these results, the same analysis was subsequently applied to describe the mechanical response of common carotid arteries excised from a mouse model (mgR/mgR) of Marfan syndrome and tested under biaxial loading. These animal models express fibrillin-1, a microfibrillar glycoprotein that appears to stabilize elastic fibers mechanically, at only 15 to 25% of normal levels. This genetic modification is usually associated with higher rates of thoracic aortic aneurysm (TAA). Elastase was used to degrade elastin in common carotid arteries excised at 7 to 9 weeks of age. In vitro biaxial mechanical and functional tests performed before and after exposure to elastase revealed that the fibrillin-1 deficient arteries exhibit biomechanical characteristics consistent with significant structural integrity of elastin. These findings support the hypothesis that it is a premature fatigue-induced damage to otherwise competent elastic fibers that render arteries in Marfan syndrome patients susceptible to lethal dilatation, dissection, and rupture