Numerical evaluation reveals the effect of branching morphology on vessel transport properties during angiogenesis

Abstract

Blood flow governs transport of oxygen and nutrients into tissues. Hypoxic tissues secrete VEGFs to promote angiogenesis during development and in tissue homeostasis. In contrast, tumors enhance pathologic angiogenesis during growth and metastasis, suggesting suppression of tumor angiogenesis could limit tumor growth. In line with these observations, various factors have been identified to control vessel formation in the last decades. However, their impact on the vascular transport properties of oxygen remain elusive. Here, we take a computational approach to examine the effects of vascular branching on blood flow in the growing vasculature. First of all, we reconstruct a 3D vascular model from the 2D confocal images of the growing vasculature at postnatal day 5 (P5) mouse retina, then simulate blood flow in the vasculatures, which are obtained from the gene targeting mouse models causing hypo- or hyper-branching vascular formation. Interestingly, hyper-branching morphology attenuates effective blood flow at the angiogenic front, likely promoting tissue hypoxia. In contrast, vascular hypo-branching enhances blood supply at the angiogenic front of the growing vasculature. Oxygen supply by newly formed blood vessels improves local hypoxia and decreases VEGF expression at the angiogenic front during angiogenesis. Consistent with the simulation results indicating improved blood flow in the hypo-branching vasculature, VEGF expression around the angiogenic front is reduced in those mouse retinas. Conversely, VEGF expression is enhanced in the angiogenic front of hyper-branching vasculature. Our results indicate the importance of detailed flow analysis in evaluating the vascular transport properties of branching morphology of the blood vessels.

Topological evolution of sprouting vascular networks: from day-by-day analysis to general growth rules

“…In previous literature, the complexity of vascular networks has been typically quantified in terms of the average global characteristics such as the area fraction of the vessels 48 , lacunarity 17 or the so-called branching index, i.e., the linear density of branching points along the vessels 48 . Here, we additionally focus on local morphological features of a branching network, that is on the distribution of the bifurcation angles ϕ .…”

Complex relationship among vessel diameter, shear stress and blood pressure controlling vessel pruning during angiogenesis

“…Angiogenic vascular growth is important to improve tissue hypoxia. To investigate whether vessel pruning contributes to the increase of blood flow at the angiogenic front, 3D vascular structures were reconstructed from 2D confocal images using an antibody against ICAM-II, the marker for the endothelial luminal surface as previously established (Mirzapour-Shafiyi et al , 2021). Regressing ECs integrate into neighboring vessels and leave empty sleeves with the EC basement membrane, including collagen type IV as a remnant of the existed vascular connection(Adams & Alitalo, 2007; Baeyens et al , 2016; Baluk et al , 2003; Gerhardt et al , 2003; Potente et al , 2011).…”

Deep Capillary Plexus Features in Acute Macular Neuroretinopathy: Novel Insights Based on the Anatomy of Henle Fiber Layer

“… 32 Others have shown that flow speed in the murine retina is affected by vascular branching morphology. 33 Whether the geometrical arrangement observed in capillary vortices and changes in blood viscosity secondary to oral contraceptives or viral infections impact oxygen delivery in the DCP has not yet been addressed. 34 , 35 We believe that this topic should be further studied, as it is likely to expand our understanding of the mechanisms involved in some AMN cases.…”