Vascular physiology: effects of vascular smooth muscle alteration on arterial wall biomechanics

This thesis aims at better understanding the role played by vascular smooth muscle cells (VSM) in the biomechanics of the arterial wall. Current models assume that under maximal vasodilation VSM carry no load, or the so-called "active stress" is zero. Biomechanical tests on arterial segments, where VSM cells were either chemically removed or structurally weakened have shown that VSM are playing a determinant role in the biomechanical properties of the arterial wall and carry important load even when maximally dilated. Based on these results a new model of the arterial wall biomechanics is proposed that takes into account the passive structure of the arterial wall constituents. The entire thesis consists of three distinct studies, either published or submitted and under review for publication. The first paper presents the effects of decellularization on the biomechanical properties of porcine common carotid arteries. The decellularization was performed by a detergent-enzymatic procedure, which preserves the extracellular matrix scaffold. Rupture tests were conducted. Inner diameter and wall thickness were measured by echotracking during pressure inflation from 10 to 145 mmHg. Distensibility and incremental elastic modulus were computed. At 10 mmHg, mean inner diameter of decellularized arteries was substantially higher than controls, whereas both decellularized and control arteries reached the same internal diameter value at 145 mmHg. Removing cellular elements from media lead to changes in arterial dimensions. The incremental elastic modulus increased, and the collagen fibers engaged more rapidly during inflation, thus yielding a stiffer vessel. Distensibility and compliance were therefore significantly lower in decellularized vessels, reaching a factor three reduction in the physiological range of pressures. The conclusion of this paper is that decellularization yields vessels able to withstand high inflation pressures with, however, markedly different geometrical and biomechanical properties. The second paper proposes an interpretation of the data collected in the experiments conducted in the first paper. This initial work on decellularized arteries revealed the existence of significant residual stresses within the arterial wall, which are released upon chemical removal of vascular smooth muscle in normal arteries causing substantial radial expansion. Hence, the often-used Hill's model describing active and passive stresses within the wall does not hold true, because the existence of prestresses precludes the fundamental assumption of zero active stress when the vascular smooth muscle is inactive. A new mathematical model based on a modified Hill's model was developed, where the total wall elastin is partitioned in two parts: one in-parallel to vascular smooth muscle and collagen and one connected in-series with vascular smooth muscle. Based on experimental evidences, compressive prestresses were assumed to exist on the parallel elastic component and tensile prestresses on the series elastic component. Further, it was assumed that the elastic constants of elastin and collagen and the statistical description of collagen engagement are not affected by decellularization. Excellent fits of the pressure-diameter curves of normal and decellularized arteries were obtained. The model predicts that the majority of elastin is in-series with the vascular smooth muscle (74±8%) and thus only about one-fourth of elastin acts in parallel to the vascular smooth muscle. The conclusion of this paper is that correct biomechanical modeling of the arterial wall requires the knowledge of the zero stress state of both the series and parallel elastic components. The third and last paper analyzes the effects of cytoskeleton destruction, after administration of Cytochalasin D, on the biomechanical properties of porcine common carotids. Compared to untreated, maximally dilated controls, Cytochalasin D-treated arteries have shown a marked increase in compliance in the elastin-dominated, 10-150 mmHg, pressure range. After weakening the vascular smooth muscle stress-bearing cytoskeleton by Cytochalasin D the artery would expand, reaching a new equilibrium state. This study brings further evidence that VSM is under tension, even when it is under zero load and at maximal vasodilation. This residual tension was released upon partial destruction of the cytoskeleton with Cytochalasin D. From a biomechanical standpoint, this means that the Zero Stress States of the in series and parallel elastic components are substantially different.


Related material