Towards a Unified Multi-Scaled Theoretical-Experimental Paradigm for Characterizing Vascular Remodeling

Vascular remodeling plays a key role in many physiological and pathophysiological processes, as well as the success or failure of many clinical interventions; examples include vascular development and aging, hypertension and atherosclerosis, and restenosis of vascular grafts. Despite the explosion of information on vascular remodeling, from the molecular level to the tissue level, attempts at integrating these data into a predictive multi-scale model are still in their infancy. Humphrey and Rajagopal said well that in order to capture the salient features of these remodeling processes ‘one must track local balances or imbalances in the continual production, removal, [and remodeling] of individual constituents, the mechanical state in which the constituents are formed, and how these constituents are organized’. Abdominal aortic aneurysms (AAA’s) provide a good illustration of the need for a multi-scaled microstructurally-motivated mathematical model. During progression of AAA’s, circumferential expansion, vessel wall thinning and axial lengthening are coincident with a progressive loss of elastin and smooth muscle and decrease in glycosaminoglycans, with mature aneurysms consisting primarily of collagen and fibroblasts; thus, AAA’s experience spatial and temporal variations in their geometry, microstructural content and organization, and applied loads. To develop a predictive model for vascular remodeling, the complex interplay between evolving material behavior (via changes in microstructural content and organization) and applied loads, which determine the local mechanical environment and the mechano-biological response to this changing mechanical environment, must be incorporated.