May 2, 2017
Whitaker Hall Auditorium
"Central Artery Stiffness in Aging and Disease"
Central arterial stiffening is both an indicator and an initiator of cardiovascular disease, and aging is a ubiquitous cause of stiffening. In this talk, we will discuss the utility of biomechanical models in understanding particular effects of arterial stiffening on systemic hemodynamics and we will discuss advantages of using mouse models to obtain detailed longitudinal information on regional variations in arterial wall properties. In particular, we will focus on delineating intrinsic material and structural stiffness as a function of location along the aorta and we will show results from 3-D computational simulations of the hemodynamics that account for interactions between the blood and regional wall properties. Amongst the different findings, one emerging concept is that mechano-adaptive responses appear to favor the maintenance of material stiffness near normal values while offsetting increased hemodynamic loads or genetic defects with changes in structural stiffness. Additionally, however, subsequent inflammation-mediated remodeling can lead to maladaptive responses, with significant consequences on both the local mechanobiology and the global physiology.
Jay D. Humphrey
John C. Malone Professor and Chair
Department of Biomedical Engineering
Yale University, New Haven, CT
"I have 30 years of experience in the field of continuum biomechanics, with primary interest in vascular mechanics and mechanobiology. My lab has considerable experience in the design and construction of novel computer-controlled multiaxial test systems, measurement of vascular mechanical properties, computer-aided histological characterizations, nonlinear constitutive formulations, measurement of in vivo hemodynamics, and computational biomechanics (mainly finite elements). We have formulated a unique "Constrained Mixture Theory" for arterial growth and remodeling (G&R) that has provided significant insight into the biomechanics of arterial adaptations to altered hemodynamics as well as aneurysmal enlargement, vein graft maladaptation, and tissue engineered vascular graft development. We have also developed both a finite element model of the effects of pooled glycosaminoglycans within the aortic wall, a histopathological characteristic unique to thoracic aortic aneurysms and dissections, and a fluid-solid-interaction model of the aortic tree that enables hypothesis generation and testing as well as experimental design. Finally, we have considerable experience with rodent models of vascular disease, including genetically modified, pharmacological, and surgical. We recently published, for example, a first of its kind comparative biomechanical phenotyping of common carotid arteries from 7 different mouse models that suggested that mural cells attempt to maintain material stiffness constant."