scholarly journals Association between erythrocyte dynamics and vessel remodelling in developmental vascular networks

Author(s):  
Qi Zhou ◽  
Tijana Perovic ◽  
Ines Fechner ◽  
Lowell T. Edgar ◽  
Peter R. Hoskins ◽  
...  

AbstractSprouting angiogenesis is an essential vascularisation 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 polarise and migrate in response to flow-induced wall shear stress (WSS). However, the question of how the presence of erythrocytes (well-known as RBCs) and their haemodynamics impact affects 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 depletion, 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.SummaryRecent studies demonstrate that during sprouting angiogenesis, blood flow provides crucial hydrodynamic cues (e.g. wall shear stress) for the remodelling of primitive plexuses towards a functional network. Notwithstanding, the role of RBCs in this process remains poorly understood. We report on the inherent heterogeneity of RBC perfusion within primitive vasculatures, and uncover a strong association between RBC depletion and vessel regression. Our work indicates the essential role of RBC dynamics in the establishment of regional WSS differences driving vascular remodelling. The RBC-driven process of pruning cell-depleted vessels not only importantly contributes to the optimal patterning of vascular networks during development, but also provides a remodelling mechanism to support clinical findings of microangiopathic complications associated with impaired RBC deformability in diseases such as diabetes mellitus and hypertension.

2019 ◽  
Vol 316 (1) ◽  
pp. C92-C103 ◽  
Author(s):  
Hojin Kang ◽  
Zhigang Hong ◽  
Ming Zhong ◽  
Jennifer Klomp ◽  
Kayla J. Bayless ◽  
...  

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.


2011 ◽  
Vol 91 (1) ◽  
pp. 327-387 ◽  
Author(s):  
Jeng-Jiann Chiu ◽  
Shu Chien

Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.


Author(s):  
F. Kh. Tazyukov ◽  
H. A. Khalaf ◽  
Jafar M. Hassan

The problems of non-Newtonian blood flow through a stenosed artery are solved numerically using Finite Volume Method where the non-Newtonian rheology of the flowing blood is characterised by the Generalised Power-law, Carreau-Yasuda and Cross models. In view of the haemodynamical mechanisms related to atherosclerosis formation and the role of the wall shear stress in initiating and further developing of the disease, the investigation is focused on the two-dimensional flow field and in particular on the distribution of the wall shear stress in the vicinity of the stenosis. A comparison is made between the effects of each rheological model on the aforementioned parameters for different Re number.


2008 ◽  
Vol 2 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Cibele M Prado ◽  
Marcos A Rossi

This review is based on recently published data from our laboratory. We investigated the role of hypertension and laminar flow, hypercholesterolemia and laminar flow and turbulent blood flow/low wall shear stress, and turbulent blood flow/low wall shear stress associated with hypercholesterolemia on aorta remodeling of rats feeding normal diet or hypercholesterolemic diet. Our findings suggest that increased circumferential wall tension due to hypertension plays a key role in the remodeling through biomechanical effects on oxidative stress and increased TGF-β expression; the remodeling observed in the presence of hypercholesterolemia could be initiated by oxidative stress that is involved in several processes of atherogenesis and this remodeling is more pronounced in the presence of turbulent blood flow/low wall shear stress.


2020 ◽  
Vol 59 (SK) ◽  
pp. SKKE16 ◽  
Author(s):  
Ryo Nagaoka ◽  
Kazuma Ishikawa ◽  
Michiya Mozumi ◽  
Magnus Cinthio ◽  
Hideyuki Hasegawa

2021 ◽  
Author(s):  
Chandan Kumawat ◽  
Bhupendra Kumar Sharma ◽  
Khalid Saad Mekheimer

Abstract A two-phase blood flow model is considered to analyze the fluid flow and heat transfer in a curved tube with time-variant stenosis. In both core and plasma regions, the variable viscosity model ( Hematocrit and non linear temperature-dependent, respectively) is considered. A toroidal coordinate system is considered to describe the governing equations. The perturbation technique in terms of perturbation parameter ε is used to obtain the temperature profile of blood flow. In order to find the velocity, wall shear stress and impedance profiles, a second-order finite difference method is employed with the accuracy of 10−6 in the each iteration. Under the conditions of fully-developed flow and mild stenosis, the significance of various physical parameters on the blood velocity, temperature, wall shear stress (WSS) and impedance are investigated with the help of graphs. A validation of our results has been presented and comparison has been made with the previously published work and present study, and it revels the good agreement with published work. The present mathematical study suggested that arterial curvature increase the fear of deposition of plaque (atherosclerosis), while, the use of thermal radiation in heat therapies lowers this risk. The positive add in the value of λ1 causes to increase in plasma viscosity; as a result, blood flow velocity in the stenosed artery decreases due to the assumption of temperature-dependent viscosity of the plasma region. Clinical researchers and biologists can adopt the present mathematical study to lower the risk of lipid deposition, predict cardiovascular disease risk and current state of disease by understanding the symptomatic spectrum, and then diagnose patients based on the risk.


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