Estimation of Shear Stress Heterogeneity along Capillary Segments in Angiogenic Rat Mesenteric Microvascular Networks

Abstract

Fluid shear stress has been identified as an important player in regulating endothelial cell behavior and angiogenesis, defined as the sprouting of new blood vessels from existing vessels. However, the correlative or functional linking of shear stress to vessel‐specific endothelial cell dynamics requires a better understanding of the shear stress values at the capillary level in microvascular networks. Critical questions remain unanswered. What is the shear stress experienced by endothelial cells along capillaries? Do all capillaries experience similar shear stress magnitudes? Can variations in shear stress along different capillary segments explain vessel‐specific responses? The objective of this project was to estimate shear stress values in regions of angiogenic microvascular networks. Rat mesenteric tissues were harvested from adult male Wistar rats post the stimulation of angiogenesis via 48‐80 mast cell degranulation. Microvascular networks were identified by perfusion of a 40kDa fixable dextran prior to harvesting and immunolabelling for PECAM. Dextran presence identified perfused segments along the hierarchy of microvascular networks, which were characterized by increased vessel density indicative of angiogenesis. Two representative network regions with arteriole input and venule output vessels were selected for analysis. Vessel segments were defined by nodes, branch order position, and the measurements of lengths and diameter. Assuming an inlet pressure of 75 mmHg and outlet pressure of 10 mmHg, a network segmental Newtonian flow model was used to computationally estimate vessel‐specific shear stresses and velocities. Viscosity was set to 4 cP and assumed to be constant. For region 1, shear stresses along capillaries (diameters less than 10 microns) ranged from 0.7 to 479 dyne/cm2 (average = 57± 69 dyne/cm2). For region 2, shear stresses along capillaries ranged 0.1 to 1032 dyne/cm2 (average = 75± 94 dyne/cm2). For both regions, the maximum shear stress along capillary segments was greater than the maximum shear stress in the initial arterial branches. The high variability at the capillary level in both network regions suggests the potential for vessel‐specific stimuli. The maximum shear stresses in proximal capillary segments connecting the high‐pressure arterial sides to the lower pressure venous sides in a network were increased compared to stresses for segments in more distal network regions. The results of this study highlight the heterogeneity of shear stress experienced by endothelial cells at the capillary level in angiogenic microvascular networks and motivate questions related to how vessel‐specific hemodynamic environments regulate endothelial cell function.