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Objective: Fluid shear stress is thought to be a regulator of endothelial cell behavior during angiogenesis. The link, however, requires an understanding of stress values at the capillary level in angiogenic microvascular networks. Critical questions remain. What are the stresses? Do capillaries experience similar stress magnitudes? Can variations explain vessel‐specific behavior? The objective of this study was to estimate segment‐specific shear stresses in angiogenic networks. Methods: Images of angiogenic networks characterized by increased vascular density were obtained from rat mesenteric tissues stimulated by compound 48/80‐induced mast cell degranulation. Vessels were identified by perfusion of a 40 kDa fixable dextran prior to harvesting and immunolabeling for PECAM. Using a network flow‐based segment model with physiologically relevant parameters, stresses were computed per vessel for regions across multiple networks. Results: Stresses ranged from 0.003 to 2328.1 dyne/cm2 and varied dramatically at the capillary level. For all regions, the maximum segmental shear stresses were for capillary segments. Stresses along proximal capillaries branching from arteriole inlets were increased compared to stresses along capillaries in more distal regions. Conclusions: The results highlight the variability of shear stresses along angiogenic capillaries and motivate new discussions on how endothelial cells may respond in vivo to segment‐specific microenvironment during angiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The effect of NO on smooth muscle cell contractility is crucial in regulating vascular tone, blood flow, and O2 delivery. Quantitative predictions for interactions between the NO production rate and the myogenic response for microcirculatory blood vessels are lacking. Methods: We developed a computational model of a branching microcirculatory network with four representative classes of resistance vessels to predict the effect of endothelium‐derived NO on the microvascular pressure‐flow response. Our model links vessel scale biotransport simulations of NO and O2 delivery to a mechanistic model of autoregulation and myogenic tone in a simplified microcirculatory network. Results: The model predicts that smooth muscle cell NO bioavailability significantly contributes to resting vascular tone of resistance vessels. Deficiencies in NO seen during hypoxia or ischemia lead to a decreased vessel diameter for all classes at a given intravascular pressure. At the network level, NO deficiencies lead to an increase in pressure drop across the vessels studied, a downward shift in the pressure‐flow curve, and a decrease in the effective range of the autoregulatory response. Conclusions: Our model predicts the steady state and transient behavior of resistance vessels to perturbations in blood pressure, including effects of NO bioavailability on vascular regulation. [ABSTRACT FROM AUTHOR]

Objective Lymphatic and blood microvascular systems are critical for tissue function. Insights into the coordination of both systems can be gained by investigating the relationships between lymphangiogenesis and angiogenesis. Recently, our laboratory established the rat mesentery culture model as a novel tool to investigate multicellular interactions during angiogenesis in an intact microvascular network scenario. The objective of this study was to determine whether the rat mesentery culture model can be used to study lymphangiogenesis. Methods Mesenteric tissue windows were harvested from adult male Wistar rats and cultured for three or five days in either serum-free MEM or MEM supplemented with VEGF-C. Tissues were immunolabeled for PECAM and LYVE-1 to identify blood and lymphatic endothelial cells, respectively. Tissues selected randomly from those containing vascular networks were quantified for angiogenesis and lymphangiogenesis. Results VEGF-C treatment resulted in an increase in the density of blood vessel sprouting compared to controls by day 3. By day 5, lymphatic sprouting was increased compared to controls. Conclusions These results are consistent with in vivo findings that lymphangiogenesis lags angiogenesis after chronic stimulation and establish a tool for investigating the interrelationships between lymphangiogenesis and angiogenesis in a multisystem microvascular environment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the degree of microvascular impairment in DR using multifractal and lacunarity analyses and to compare the diagnostic ability between traditional Euclidean measures (fovea avascular zone area and vessel density) and fractal geometric features. Methods: This retrospective cross‐sectional study included a total of 143 eyes of 94 patients with different stages of DR. The retinal microvasculature was imaged by projection removed OCTA. We examined the degree of association between fractal metrics of the retinal microvasculature and DR severity. The area under the ROC curve was used to estimate the diagnostic performance. Results: With increasing DR severity, the multifractal spectrum shifted toward the left bottom and exhibited less left skewness and asymmetry. The vessel density, multifractal features, and lacunarity measured from the DCP were strongly associated with DR severity. The multifractal feature D5 showed the highest diagnostic ability. The combination of multifractal features further improved the discriminating power. Conclusions: Multifractal and lacunarity analyses can be potentially valuable tools for assessment of microvascular impairments in DR. Multifractal geometric parameters exhibit a better discriminatory performance than Euclidean measures, particularly for detection of the early stages of DR. [ABSTRACT FROM AUTHOR]

Objective: Motivated by observations of mesenteries harvested from mice treated with tamoxifen dissolved in oil for inducible gene mutation studies, the objective of this study was to demonstrate that microvascular growth can be induced in the avascular mouse mesentery tissue. Methods: C57BL/6 mice were administered an IP injection for five consecutive days of: saline, sunflower oil, tamoxifen dissolved in sunflower oil, corn oil, or peanut oil. Results: Twenty‐one days post‐injection, zero tissues from saline group contained branching microvascular networks. In contrast, all tissues from the three oils and tamoxifen groups contained vascular networks with arterioles, venules, and capillaries. Smooth muscle cells and pericytes were present in their expected locations and wrapping morphologies. Significant increases in vascularized tissue area and vascular density were observed when compared to saline group, but sunflower oil and tamoxifen group were not significantly different. Vascularized tissues also contained LYVE‐1‐positive and Prox1‐positive lymphatic networks, indicating that lymphangiogenesis was stimulated. When comparing the different oils, vascularized tissue area and vascular density of sunflower oil were significantly higher than corn and peanut oils. Conclusions: These results provide novel evidence supporting that induction of microvascular network growth into the normally avascular mouse mesentery is possible. [ABSTRACT FROM AUTHOR]