Mechanisms of Arterial Remodeling in Hypertension

Abstract

Diverse data collected over the past 4 decades suggest the existence of a mechanical homeostasis across multiple length and time scales in the vasculature. For example, 1 stress fibers within endothelial and vascular smooth muscle cells appear to disassemble and then reassemble in a mechanically preferred manner when perturbed from a normal value of mechanical stress or strain; focal adhesions in smooth muscle cells and fibroblasts tend to increase in area in response to local increases in mechanical loading so as to maintain the stress constant at a preferred value; fibroblasts tend to increase the tractions that they exert on the extracellular matrix when external loads are decreased from a preferred value, thus suggesting an attempt to enforce a "tensional homeostasis"; vascular smooth muscle cells tend to relengthen to their normal, preferred values when an arteriole is forced into a vasoconstricted state for an extended period; and arteries tend to decrease in caliber in response to sustained decreases in flow-induced wall shear stress, to increase in thickness in response to sustained increases in pressureinduced circumferential stress, and to lengthen in response to extension-induced increases in axial stress. Although changes in the cytoskeleton and integrins occur within minutes, changes at the cell-cell and cell-matrix levels occur over hours, and those at the vessel level occur over days to weeks or months. Hence, despite marked differences in length scales (dimensions from nanometers to centimeters) and time scales (durations from minutes to months), mechanobiological control mechanisms in the vasculature tend to restore values of stress or strain toward preferred (homeostatic) values in response to diverse perturbations from normal. 2-5 Biomechanics and mechanobiology thus play key roles in vascular development, tissue maintenance in maturity, normal adaptations, aging, disease progression, and responses to injury or clinical interventions.A current challenge in hypertension research is to understand how mechanobiological mechanisms at molecular and cellular levels (eg, altered turnover of collagen) manifest at tissue and organ levels and, conversely, how mechanical loads at tissue and organ levels (eg, increased pulse pressure) are sensed by molecular structures and result in altered gene expression. To gain increased understanding, we can exploit lessons learned from all areas of vascular research, because it appears that the same fundamental cell-mediated mechanisms govern diverse cases of vascular growth (ie, change in mass) and remodeling (ie, change in structure) via the reorganization and/or turnover of cells and extracellular matrix in evolving biomechanical states. 1

Computational Simulation of the Adaptive Capacity of Vein Grafts in Response to Increased Pressure

“…While knowledge of the homeostatic state can suggest the final state of an adaptation [42], cell-mediated G&R models can shed light on mechanisms of these adaptations. Some previous attempts at modeling vein graft adaptations have prescribed changes in geometry as functions of time and stress [17,43].…”

Differential impact of local stiffening and narrowing on hemodynamics in repaired aortic coarctation: an FSI study

“…Patients with (repaired) aortic coarctation might have intrinsic structural defects in extracellular matrix proteins due to genetic defects [42], and their aorta has been subjected to growth and remodeling [16,23] with adaptions in shape and material properties. In particular for the case of aortic coarctation, wall thickening is often observed along with a decrease in compliance of the proximal aorta due to prolonged hypertension [8,27].…”

Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

“…Finally, increased wall stress causes pathologic remodeling in systemic arteries. [73][74][75][76][77] Note that intravascular pressure is not the only plausible relevant mechanical force. The cross-sectional area of the pulmonary vascular bed is presumably reduced with PVHincreased PVR, implying (absent lower flow) that shear stress is increased.…”