Modeling effects of axial extension on arterial growth and remodeling.

Diverse mechanical perturbations elicit arterial growth and remodeling responses that appear to optimize structure and function so as to promote 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.