Vessel-Specific Shear Stress Distribution and Heterogeneity in Angiogenic Rat Mesenteric Microvascular Networks

Abstract

Fluid shear stress has been identified as an important player in regulating endothelial cell behaviors 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. Representative network regions with arteriole input and venule output vessels were selected for analysis. Vessel segments were defined by adjacent nodes, 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. In the results, shear stresses along vascular segments in 3 medium microvascular regions ranged from 0.1 to 1114.3 dyne/cm2 (average = 81.3 ± 3.5 dyne/cm2), in 4 small regions ranged from 0.1 to 518.7 dyne/cm2 (average = 61 ± 3.4 dyne/cm2), and in 1 large region ranged from 0.003 to 2328.1 dyne/cm2 (average = 39.8 ± 1.6 dyne/cm2). For all regions, the highest shear stress values located at capillary segments, defined as vascular segments with diameters lower than 10 μm. As segment diameters increased, the matched maximum shear stresses decreased accordingly. Also, the high heterogeneity of shear stresses in capillaries indicates the possibility for segment-specific regulation. For 3 medium regions, shear stresses along proximal capillaries branching from arteriolar inlets to venular outlets were higher than stresses along capillaries in regions distal to inlets and outlets. The results highlight the variability of segment-specific shear stresses along capillaries in microvascular regions and motivate research looking into how endothelial cells respond to segment-specific microenvironment and regulation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.