Impact of Residual Stretch and Remodeling on Collagen Engagement in Healthy and Pulmonary Hypertensive Calf Pulmonary Arteries at Physiological Pressures

Abstract

Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries’ histological changes, in vivo pressure–diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized. To further understand the mechanical behavior of the proximal PAs under physiological conditions, this study computed the residual stretch and the in vivo circumferential stretch state in the main pulmonary arteries in both control and hypertensive calves by using in vitro and in vivo artery geometry data, and modeled the impact of residual stretch and arterial remodeling on the in vivo circumferential stretch distribution and collagen engagement in the main pulmonary artery. We found that the in vivo circumferential stretch distribution in both groups was nonuniform across the vessel wall with the largest stretch at the outer wall, suggesting that collagen at the outer wall would engage first. It was also found that the circumferential stretch was more uniform in the hypertensive group, partially due to arterial remodeling that occurred during their hypoxic treatment, and that their onset of collagen engagement occurred at a higher pressure. It is concluded that the residual stretch and arterial remodeling have strong impact on the in vivo stretch state and the collagen engagement and thus the mechanical behavior of the main pulmonary artery in calves.

The Role of Wall Shear Stress in the Assessment of Right Ventricle Hydraulic Workload

“…15 This adverse remodeling ultimately affects the arteries' mechanical properties. 16 An elevated resistance in the distal arteries causes a pressure increase in the large proximal vasculature, leading to proximal arterial remodeling in the form of increased arterial stiffness and thickness. This compromises the proximal vasculature's role as a hydraulic damper to the distal vessels, 17,18 causing distal endothelial cells to be exposed to nonphysiological pulse pressure and initiating a destructive cycle.…”

Validation of an arterial constitutive model accounting for collagen content and crosslinking

“…Note that due to residual strain, the artery under no-load state is under tension at the outer wall [27,44,45]. A combination of a longitudinal stretch (140% in this study) and a small intramural pressure can result in an approximate stretch-free state at the outer wall of the artery [27].…”

“…Instead, changes in the extracellular matrix (e.g., elastin and collagen) can be dramatic. Elastin, which bears most of the mechanical load in the low stretch region [4,25–27], was found to increase elastic modulus significantly in a neonatal calf model of hypoxic pulmonary hypertension (HPH) and to contribute importantly to increased arterial stiffness [4]. In the adult mouse model of HPH, however, elastin was not found to change significantly; instead, collagen accumulation was found to correlate to the PA elastic modulus in the physiological strain range [3,5].…”

Urotensin II contributes to collagen synthesis and up-regulates Egr-1 expression in cultured pulmonary arterial smooth muscle cells through the ERK1/2 pathway

“…[21]. Collagen is the main component of the extracellular matrix, and it contributes to vascular tension resistance and elasticity [22]. Specifically, collagen I is associated with tension in vessel walls, and collagen III is associated with the elasticity of vessel walls [23].…”