Mechanics of Atherosclerosis, Hypertension Induced Growth, and Arterial Remodeling

In order to create informed predictive models that capture artery dependent responses during atherosclerosis progression and the long term response to hypertension, one needs to know the structural, biochemical and mechanical properties as a function of time in these diseased states. In the case of hypertension more is known about the mechanical changes; while, less is known about the structural changes over time. For atherosclerotic plaques, more is known about the structure and less about the mechanical properties. We established a congruent multi-scale model to predict the adapted salient arterial geometry, structure and biochemical response to an increase in pressure. Geometrical and structural responses to hypertension were then quantified in a hypertensive animal model. Eventually this type of model may be used to predict mechanical changes in complex disease such as atherosclerosis. Thus for future verification and implementation we experimentally tested atherosclerotic plaques and quantified composition, structure and mechanical properties. Using the theoretical models we can now predict arterial changes in biochemical concentrations as well as salient features such as geometry, mass of elastin, smooth muscle, and collagen, and circumferential stress, in response to hemodynamic loads. Using an aortic coarctation model of hypertension, we found structural arterial responses differ in the aorta, coronary and cerebral arteries. Effects of elevated pressure manifest first in the central arteries and later in distal muscular arteries. In the aorta, there is a loss and then increase of cytoskeleton actin fibers, production of fibrillar collagen and elastin, hyperplasia or hypertrophy with nuclear polypoid, and recruitment of hemopoeitic progenitor cells and monocytes. In the muscular coronary, we see similar changes albeit it appears actin fibers are recruited and collagen production is only increased slightly in order to maintain constant the overall ratio of ~55 percent. In the muscular cerebral artery, despite a temporary loss in actin fibers there is little structural change. Contrary to hypertensive arteries, characterizing regional stiffness in atherosclerotic plaques has not been done before. Therefore, experimental testing on atherosclerotic plaques of Apolipoprotein E Knockout mice was performed and revealed nearly homogenously lipidic plaques with a median axial compressive stiffness value of 1.5 kPa.