Association between erythrocyte dynamics and vessel remodelling in developmental vascular networks

Abstract

Sprouting angiogenesis is an essential vascularization mechanism consisting of sprouting and remodelling. The remodelling phase is driven by rearrangements of endothelial cells (ECs) within the post-sprouting vascular plexus. Prior work has uncovered how ECs polarize and migrate in response to flow-induced wall shear stress (WSS). However, the question of how the presence of erythrocytes (widely known as red blood cells (RBCs)) and their impact on haemodynamics affect vascular remodelling remains unanswered. Here, we devise a computational framework to model cellular blood flow in developmental mouse retina. We demonstrate a previously unreported highly heterogeneous distribution of RBCs in primitive vasculature. Furthermore, we report a strong association between vessel regression and RBC hypoperfusion, and identify plasma skimming as the driving mechanism. Live imaging in a developmental zebrafish model confirms this association. Taken together, our results indicate that RBC dynamics are fundamental to establishing the regional WSS differences driving vascular remodelling via their ability to modulate effective viscosity.

Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas

“…Type I transmembrane glycoprotein present in the apical/luminal endothelial cell membrane ICAM2 masks highlight vessel segments undergoing remodeling. It mediates adhesive interactions important for antigen-specific immune response [11,18,19] CLDN5 (claudin 5)…”

“…Collagen IV is the most abundant structural BM component and is essential for BM integrity but not initial BM formation [11,19,21] Endoglin (ENG) also known as CD105…”

Traffic Patterns of the Migrating Endothelium: How Force Transmission Regulates Vascular Malformation and Functional Shunting During Angiogenic Remodelling

“…We modelled blood as a Newtonian fluid and Poiseuille flow, but in reality blood exhibits many important attributes of non-Newtonian fluids. Specifically, the inclusion of erythrocytes within our network haemodynamics may be crucial next step, as we have previously identified an important association between erythrocyte dynamics and vascular remodelling due to plasma skimming effects ( Zhou et al, 2021 ). Our current model also included a simplistic representation of EC flow-migration coupling as well, with agents migration governed by which we kept constant in this study.…”

Red blood cell dynamics in extravascular biological tissues modelled as canonical disordered porous media

“…The immersed-boundary-lattice-Boltzmann method (IB-LBM [27]) is employed to simulate cellular blood flow as a suspension of deformable RBCs. The numerical model is implemented in the parallel flow simulator HemeLB [39] (open source at https://github.com/hemelb-codes/hemelb), which has been successfully applied to cellular simulation in complex and sparse geometries (e.g., realistic microvasculature [4]). The 3D fluid flow governed by the Navier-Stokes equations is solved by the lattice-Boltzmann method (LBM) with standard D3Q19 lattice [40], BGK collision operator [41], Guo's forcing scheme [42] and the Bouzidi-Firdaouss-Lallemand (BFL) implementation of no-slip condition at the walls [43].…”

“…Significant progress in computational modelling has been made over recent years to elucidate the complex behaviour of blood flow in physiological environments, e.g ., the small-vessel network in the brain [1, 2, 3], in the eye [4, 5], in tumours [6], and in microaneurysms [7]. However, the flow and transport of blood and solutes in other ( e.g ., extravascular) types of biological media with vital function, such as the intervillous space (IVS) of the human placenta featuring a highly disordered network of pores and flow passages of size comparable to that of red blood cells (RBCs), remain poorly understood [8, 9].…”