Structural Remodeling of the Mouse Gracilis Artery: Coordinated Changes in Diameter and Medial Area Maintain Circumferential Stress

Abstract

Objectives Vascular networks respond to chronic alterations in blood supply by structural remodeling. Previously, we showed that blood flow changes in the mouse gracilis artery lead to transient diameter increases, which can generate large increases in circumferential wall stress. Here, we examine the associated changes in the medial area of the arterial wall and the effects on circumferential wall stress. Methods To induce blood flow changes, one of the two feeding vessels to the gracilis artery was surgically removed. At 7 to 56 days after blood flow interruption, the vasculature was perfused with India ink for morphological measurements, and processed for immuno-cytochemistry to mark the medial cross-section area. Theoretical simulations of hemodynamics were used to analyze the data. Results During adaptive increases in vessel diameter, increases in medial area were observed, most strongly in the middle region of the artery. Simulations showed that this increase in medial area limits the increase in estimated circumferential stress during vascular adaptation to less than 50%, in contrast to an increase of up to 250% if the medial area had remained unchanged. Conclusions During vascular adaptation, increases in circumferential stress are limited by growth of the media coordinated with diameter changes.

Aortic pulse pressure homeostasis emerges from physiological adaptation of systemic arteries to local mechanical stresses

“…The adaptive rules of the present work (Eq. 3) were first developed by Nguyen et al (46), who assumed that chronic adaptation is functionally similar to the acute shear stress-induced vasodilation and wall stress-induced vasoconstriction of muscular arteries (3,17,20,24,60) and microvessels (28,55,56,66). These adaptive rules were consistent with reported mechanisms of endothelial mechanotransduction (7) and observations from human clinical studies (9,37,39).…”

“…These parameters relate to mechanobiology, with ␣ being the chronic analog of the acute shearinduced dilation sensitivity measured in vitro (28). Instead of assuming mechanical stress set points (7,17,20,55,60,66), the present balance point approach provides a means to integrate research focused on vascular biomechanics with research focused on vascular mechanobiology.…”

“…Taken together, reported changes in arterial compliance in response to three disparate perturbations were reproduced by the model. In each case, reported observations now can be attributed to the interaction of three well-documented adaptive responses (7,17,20,24,43,47,60,82) approximated by Eq. 3.…”

“…It is exceedingly difficult to control endothelial shear stress and wall circumferential stress in vivo. Adaptation-induced changes in radius, wall thickness, or stiffness affect mechanical stresses (9,17,37,39,75), even when luminal pressure and flow can be maintained (3,38,43,66). The inability to make mechanical stresses controlled, independent variables in vivo is an inescapable consequence of arterial growth and remodeling (22,55).…”

Toward Functional Revascularization: Regulation of Vascular Network Remodeling Through Altered Hemodynamics

“…Therefore, we chose to focus on the two entrance regions to isolate the influence of flow reversal alone, without differences in the relative magnitude of an acute increase in shear stress. Importantly, the spatial variations observed here are not related to hypoxia and metabolic signaling as has been shown in a saphenous artery excision model (284,285). The differential hypoxic environment across the muscle in the saphenous artery excision model can be seen in the increased capillary density within the saphenous entrance region (143) that is not present in our model (Online Figure 5.VI).…”