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SUMMARY We implemented a constrained mixture model of arterial growth and remodeling in a nonlinear finite element framework to facilitate numerical analyses of diverse cases of arterial adaptation and maladaptation, including disease progression, resulting in complex evolving geometries and compositions. This model enables hypothesis testing by predicting consequences of postulated characteristics of cell and matrix turnover, including evolving quantities and orientations of fibrillar constituents and nonhomogenous degradation of elastin or loss of smooth muscle function. The nonlinear finite element formulation is general within the context of arterial mechanics, but we restricted our present numerical verification to cylindrical geometries to allow comparisons with prior results for two special cases: uniform transmural changes in mass and differential growth and remodeling within a two-layered cylindrical model of the human aorta. The present finite element model recovers the results of these simplified semi-inverse analyses with good agreement. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Elucidating regional material properties of arterial tissue is fundamental to predicting transmural stresses and understanding how tissue stiffness influences cellular responses and vice versa. Atomic force microscopy (AFM) was used to measure point-wise the axial compressive stiffness of healthy aortas and atherosclerotic plaques at micron level separation distances. Cross sections of plaques were obtained from a widely used animal model of atherosclerosis (ApoE-/- mice). Median point-wise values of material stiffness were 18.7 and 1.5 kPa for the unloaded healthy wall (n = 25 specimens) and plaque (n = 18), respectively. When the healthy wall was distended uniformly during AFM testing, two mechanically distinct populations emerged from comparisons of normal cumulative distributions, with median values of 9.8 and 76.7 kPa (n = 16). The higher values of stiffness may have been due to extended elastin, which was not present in the plaques. Rather, most plaques were identified via standard and immunofluorescent histology to be largely lipid laden, and they exhibited a nearly homogeneous linear elastic behavior over the small AFM indentations. Understanding the mechanics and mechanobiological factors involved in lesion development and remodeling could lead to better treatments for those lesions that are vulnerable to rupture. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The vasculature consists of a complex network of vessels ranging from large arteries to arterioles, capillaries, venules, and veins. This network is vital for the supply of oxygen and nutrients to tissues and the removal of carbon dioxide and waste products from tissues. Because of its primary role as a pressure-driven chemomechanical transport system, it should not be surprising that mechanics plays a vital role in the development and maintenance of the normal vasculature as well as in the progression and treatment of vascular disease. This review highlights some past successes of vascular biomechanics, but emphasizes the need for research that synthesizes complementary advances in molecular biology, biomechanics, medical imaging, computational methods, and computing power for purposes of increasing our understanding of vascular physiology and pathophysiology as well as improving the design of medical devices and clinical interventions, including surgical procedures. That is, computational mechanics has great promise to contribute to the continued improvement of vascular health. [Copyright &y& Elsevier]

Abstract: Arteries exhibit a remarkable ability to adapt to diverse genetic defects and sustained alterations in mechanical loading. For example, changes in blood flow induced wall shear stress tend to control arterial caliber and changes in blood pressure induced circumferential wall stress tend to control wall thickness. We submit, however, that the axial component of wall stress plays a similarly fundamental role in controlling arterial geometry, structure, and function, that is, compensatory adaptations. This observation comes from a review of findings reported in the literature and a comparison of four recent studies from our laboratory that quantified changes in the biaxial mechanical properties of mouse carotid arteries in cases of altered cell-matrix interactions, extracellular matrix composition, blood pressure, or axial extension. There is, therefore, a pressing need to include the fundamental role of axial wall stress in conceptual and theoretical models of arterial growth and remodeling and, consequently, there is a need for increased attention to evolving biaxial mechanical properties in cases of altered genetics and mechanical stimuli. [Copyright &y& Elsevier]

Abstract: Three recent studies reveal that the unloaded length of a carotid artery increases significantly and rapidly in response to sustained increases in axial extension. Moreover, such lengthening involves an “unprecedented” increase in the rate of turnover of cells and matrix. Although current data are not sufficient for detailed biomechanical analyses, we present general numerical simulations that are consistent with the reported observations and support the hypothesis that rates of turnover correlate with the extent that stresses are perturbed from normal. In particular, a 3-D analysis of wall stress suggests that moderate (15%) increases in axial extension can increase the axial stress to a much greater extent than marked (50%) increases in blood pressure increase the circumferential stress. Furthermore, such increases in axial stress can occur without inducing significant gradients in stress within the wall. Consequently, we use a new, 2-D constrained mixture model to study evolving changes in the geometry, structure, and properties of carotid arteries in response to a sustained increase in axial extension. These simulations are qualitatively similar to the reports in the literature and support the notion that the stress-free lengths of individual constituents evolve during growth and remodeling. [Copyright &y& Elsevier]

Presents the methods in identifying alternate forms of pseudostrain-energy functions for arteries. Use of theoretically motivated inequalities to check predictive capability; Use of material symmetry; Ways to identify specific forms of W.

Evidence from diverse investigations suggests that arterial growth and remodeling correlates well with changes in mechanical, stresses from their homeostatic values. Ultimately, therefore, there is a need for a comprehensive theory that accounts for changes in the 3-D distribution of stress within the arterial wall, including residual stress, and its relation to the mechanisms of mechanotransduction. Here, however, we consider a simpler theory that allows competing hypotheses to be tested easily, that can provide guidance in the development of a 3-D theory, and that may be useful in modeling solid-fluid interactions and interpreting clinical data. Specifically, we present a 2-D constrained mixture model for the adaptation of a cylindrical artery in response to a sustained alteration in flow. Using a rule-of-mixtures model for the stress response and first order kinetics for the production and removal of the three primary load-bearing constituents within the wall, we illustrate capabilities of the model by comparing responses given complete versus negligible turnover of elastin. Findings suggest that biological constraints may result in suboptimal adaptations, consistent with reported observations. To build upon this finding, however, there is a need for significantly more data to guide the hypothesis testing as well as the formulation of specific constitutive relations within the model. [ABSTRACT FROM AUTHOR]

Abstract: Recent advances in medical imaging, computational methods, and biomechanics promise to enable significant improvements in engineering-based decision making in vascular medicine, surgery, and training. To realize the potential of this approach, however, we must better synthesize the separate advances, particularly those in biofluid mechanics and arterial wall mechanics. In this paper, we describe a method for exploiting the typically small deformations experienced by arteries during the cardiac cycle while retaining essential features of the complex nonlinear, anisotropic behavior of the wall relative to unloaded configurations. In particular, we show that the well-known theory of small deformations superimposed on large can facilitate computations of fluid–solid interactions by exploiting methods familiar in linearized elasticity without compromising the description of the nonlinear wall mechanics. Indeed, the theory reveals potential errors when one simply tries to employ standard linearized results straight away. For purposes of illustration, small on large results are provided for the rabbit basilar artery and a constitutive relation for arteries recently proposed by Holzapfel and colleagues. It now remains for future studies to implement this approach in coupled fluid–solid problems. [Copyright &y& Elsevier]

Elastic and muscular arteries are distinguished by their distinct microstructures, biomechanical properties, and smooth muscle cell contractile functions. They also exhibit differential remodeling in aging and hypertension. Although regional differences in biomechanical properties have been compared, few studies have quantified biaxial differences in response to hypertension. Here, we contrast passive and active changes in large elastic and medium- and small-sized muscular arteries in adult mice in response to chronic infusion of angiotensin over 14 days. We found a significant increase in wall thickness, both medial and adventitial, in the descending thoracic aorta that associated with trends of an increased collagen:elastin ratio. There was adventitial thickening in the small-sized mesenteric artery, but also significant changes in elastic lamellar structure and contractility. An increased contractile response to phenylephrine coupled with a reduced vasodilatory response to acetylcholine in the mesenteric artery suggested an increased contractile state in response to hypertension. Overall reductions in the calculated gradients in pulse wave velocity and elastin energy storage capability from elastic-to-muscular arteries suggested a possible transfer of excessive pulsatile energy into the small-sized muscular arteries resulting in significant functional consequences in response to hypertension. [ABSTRACT FROM AUTHOR]