Modeling effects of axial extension on arterial growth and remodeling

Abstract

Diverse mechanical perturbations elicit arterial growth and remodeling responses that appear to optimize structure and function so as to achieve mechanical homeostasis. For example, it is well known that functional adaptations to sustained changes in transmural pressure and blood flow primarily affect wall thickness and caliber to restore circumferential and wall shear stresses toward normal. More recently, however, it has been shown that changes in axial extension similarly prompt dramatic cell and matrix reorganization and turnover, resulting in marked changes in unloaded geometry and mechanical behavior that presumably restore axial stress toward normal. Because of the inability to infer axial stress from in vivo measurements, simulations are needed to examine this hypothesis and to guide the design of future experiments. In this paper, we show that a constrained mixture model predicts salient features of observed responses to step increases in axial extension, including marked increases in fibrous constituent production, leading to a compensatory lengthening that restores original mechanical behavior. Because axial extension can be modified via diverse surgical procedures, including bypass operations and exploited in tissue regeneration research, there is a need for increased attention to this important aspect of arterial biomechanics and mechanobiology.

Extracellular matrix and the mechanics of large artery development

“…The model includes stress-dependent turnover and natural configurations for each component. Variations of this model have been applied to remodeling in adult arteries caused by changes in flow (Humphrey and Rajagopal 2003; Gleason et al 2004), mean pressure (Gleason and Humphrey 2004), pulse pressure (Cardamone et al 2010), spatial variations in wall components (Alford et al 2008), and axial extension (Valentin and Humphrey 2009a). A major challenge in these models is determining appropriate values for the required parameters.…”

A Multi-Layered Computational Model of Coupled Elastin Degradation, Vasoactive Dysfunction, and Collagenous Stiffening in Aortic Aging

“…We suggest that microstructurally-motivated computational models have potential to increase our understanding of these mechanisms, particularly potentially coupled effects. We present here the first such model, one that builds on our recent use of a constrained mixture model to study adaptations of normal arteries to alterations in blood flow, pressure, and stretch 106,107 . An advantage of the constrained mixture approach is that one can consider separately the individual rates of production and removal of structurally significant constituents as well as their individual deposition stretches and material properties, which is particularly useful in modeling growth and remodeling (G&R).…”

A constrained mixture model for developing mouse aorta

“…The current model does not include any provisions for investigating collagen fiber orientation. Future iterations could model the collagen as families of oriented fibers as introduced by Holzapfel et al (2000) and used in several recent mixture models (Baek et al 2006; Valentin et al 2009; Valentin and Humphrey 2009; Wan et al 2009). This would allow model predictions of collagen fiber orientation to be verified experimentally.…”

“…Each component has an individual homeostatic stretch ratio, constitutive equation and time-varying mass fraction. Constrained mixture models have been used successfully to describe the growth and remodeling of adult arteries in response to changes in blood pressure, axial length or blood flow (Valentin and Humphrey 2009; Valentin et al 2009; Wan et al 2009; Alford et al 2008; Gleason and Humphrey 2004; Gleason et al 2004), but have not yet been applied to developing vessels. Models of developing vessels are complicated by continuous and simultaneous increases in pressure, length, and flow, along with continually changing definitions of the homeostatic state.…”