scholarly journals Effects of Low and High Aneurysmal Wall Shear Stress on Endothelial Cell Behavior: Differences and Similarities

2021 ◽  
Vol 12 ◽  
Author(s):  
Sandrine Morel ◽  
Sabine Schilling ◽  
Mannekomba R. Diagbouga ◽  
Matteo Delucchi ◽  
Marie-Luce Bochaton-Piallat ◽  
...  

Background: Intracranial aneurysms (IAs) result from abnormal enlargement of the arterial lumen. IAs are mostly quiescent and asymptomatic, but their rupture leads to severe brain damage or death. As the evolution of IAs is hard to predict and intricates medical decision, it is essential to improve our understanding of their pathophysiology. Wall shear stress (WSS) is proposed to influence IA growth and rupture. In this study, we investigated the effects of low and supra-high aneurysmal WSS on endothelial cells (ECs).Methods: Porcine arterial ECs were exposed for 48 h to defined levels of shear stress (2, 30, or 80 dyne/cm2) using an Ibidi flow apparatus. Immunostaining for CD31 or γ-cytoplasmic actin was performed to outline cell borders or to determine cell architecture. Geometry measurements (cell orientation, area, circularity and aspect ratio) were performed on confocal microscopy images. mRNA was extracted for RNAseq analysis.Results: ECs exposed to low or supra-high aneurysmal WSS were more circular and had a lower aspect ratio than cells exposed to physiological flow. Furthermore, they lost the alignment in the direction of flow observed under physiological conditions. The effects of low WSS on differential gene expression were stronger than those of supra-high WSS. Gene set enrichment analysis highlighted that extracellular matrix proteins, cytoskeletal proteins and more particularly the actin protein family were among the protein classes the most affected by shear stress. Interestingly, most genes showed an opposite regulation under both types of aneurysmal WSS. Immunostainings for γ-cytoplasmic actin suggested a different organization of this cytoskeletal protein between ECs exposed to physiological and both types of aneurysmal WSS.Conclusion: Under both aneurysmal low and supra-high WSS the typical arterial EC morphology molds to a more spherical shape. Whereas low WSS down-regulates the expression of cytoskeletal-related proteins and up-regulates extracellular matrix proteins, supra-high WSS induces opposite changes in gene expression of these protein classes. The differential regulation in EC gene expression observed under various WSS translate into a different organization of the ECs’ architecture. This adaptation of ECs to different aneurysmal WSS conditions may affect vascular remodeling in IAs.

1980 ◽  
Vol 102 (4) ◽  
pp. 456-461 ◽  
Author(s):  
J. H. G. Howard ◽  
S. V. Patankar ◽  
R. M. Bordynuik

A parabolic numerical analysis procedure has been used to predict the flow in a straight, radial rotating channel of rectangular cross-section, chosen as a simple model of an impeller passage. A two equation turbulence model was employed, with alternative modifications, to include the influence of Coriolis force on turbulent kinetic energy. Alternative Coriolis force terms were evaluated by comparisons in a high-aspect-ratio duct with measured velocity, wall shear stress and turbulent viscosity. Secondary velocity predictions were checked with data from a low-aspect-ratio duct where the Coriolis modification of turbulence was found less influential than the secondary flow in the modification of side wall shear stress.


2001 ◽  
Vol 12 (11) ◽  
pp. 2300-2309 ◽  
Author(s):  
CHRISTIAN MORATH ◽  
CLAUDIUS DECHOW ◽  
INGO LEHRKE ◽  
VOLKER HAXSEN ◽  
RÜDIGER WALDHERR ◽  
...  

Abstract. Transforming growth factor—β1 (TGF-β1) overexpression plays a key role in the glomerular accumulation of extracellular matrix proteins in renal disease. Retinoids have previously been shown to significantly limit glomerular damage in rat experimental glomerulonephritis. Therefore, the effects of all-trans retinoic acid and isotretinoin on the components of the TGF-β system and extracellular matrix proteins in anti-Thy1.1-nephritis (Thy-GN) were investigated. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans retinoic acid or 40 mg/kg body wt isotretinoin (n= 9 per group) either with a pretreatment (day -2 through 8) or posttreatment protocol (day +3 through 8),i.e., starting before or after induction of Thy-GN, respectively. Urinary TGF-β1 excretion was 60% lower in all-trans retinoic acid-treated animals with Thy-GN (P< 0.025). The increase of cortical TGF-β1 gene expression in Thy-GN rats was significantly attenuated with all-trans retinoic acid and even more with isotretinoin treatment as compared with untreated animals (P< 0.025). Cortical expression of TGF receptor II, but not receptor I gene expression, was significantly lower in animals treated with all-trans retinoic acid or isotretinoin (P< 0.05). In all-trans retinoic acid—treated animals with Thy-GN, the increase of glomerular TGF-β1 protein (P< 0.008) and TGF-β1 (P< 0.025) and TGF receptor II mRNA (P< 0.015) was significantly less. Immunohistochemistry revealed less glomerular staining for TGF-β1 and TGF receptor II in the presence of all-trans retinoic acid. TGF-β1 immunostaining was not restricted to monocytes and macrophages, as indicated by double-staining. Glomerular staining for collagen IV and collagen III was less in animals treated with isotretinoin (P< 0.02 for both) in contrast to all-trans retinoic acid, whereas fibronectin remained unchanged. It was concluded that the beneficial effects of retinoids on glomerular damage are presumably due to a marked reduction in renal TGF-β1 and TGF receptor II expression.


2012 ◽  
Vol 302 (8) ◽  
pp. C1109-C1118 ◽  
Author(s):  
Jennifer M. Dolan ◽  
Fraser J. Sim ◽  
Hui Meng ◽  
John Kolega

Chronic high flow can induce arterial remodeling, and this effect is mediated by endothelial cells (ECs) responding to wall shear stress (WSS). To assess how WSS above physiological normal levels affects ECs, we used DNA microarrays to profile EC gene expression under various flow conditions. Cultured bovine aortic ECs were exposed to no-flow (0 Pa), normal WSS (2 Pa), and very high WSS (10 Pa) for 24 h. Very high WSS induced a distinct expression profile compared with both no-flow and normal WSS. Gene ontology and biological pathway analysis revealed that high WSS modulated gene expression in ways that promote an anti-coagulant, anti-inflammatory, proliferative, and promatrix remodeling phenotype. A subset of characteristic genes was validated using quantitative polymerase chain reaction: very high WSS upregulated ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motif-1), PLAU (urokinase plasminogen activator), PLAT (tissue plasminogen activator), and TIMP3, all of which are involved in extracellular matrix processing, with PLAT and PLAU also contributing to fibrinolysis. Downregulated genes included CXCL5 and IL-8 and the adhesive glycoprotein THBS1 (thrombospondin-1). Expressions of ADAMTS1 and uPA proteins were assessed by immunhistochemistry in rabbit basilar arteries experiencing increased flow after bilateral carotid artery ligation. Both proteins were significantly increased when WSS was elevated compared with sham control animals. Our results indicate that very high WSS elicits a unique transcriptional profile in ECs that favors particular cell functions and pathways that are important in vessel homeostasis under increased flow. In addition, we identify specific molecular targets that are likely to contribute to adaptive remodeling under elevated flow conditions.


2004 ◽  
Vol 74 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Kenji Takahashi ◽  
Masashi Yamazaki ◽  
Takashi Saisu ◽  
Arata Nakajima ◽  
Sumito Shimizu ◽  
...  

Author(s):  
Zijing Zeng ◽  
Hasballah Zakaria ◽  
Ramanathan Kadirvel ◽  
Yong-Hong Ding ◽  
Debra A. Lewis ◽  
...  

Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. In-vitro studies have demonstrated a correlation between the magnitude and distribution of wall shear stress (WSS) and biological response of both endothelial cells and smooth muscle cells [1–3]. In elastase induced saccular aneurysms, low WSS (below 0.5 Pa) was found to have a correlation with altered expression of biological markers [4]. Localized regions of rapid aneurysm growth in-vivo have been shown to be associated with regions where WSS is below a critical value of 0.1 Pa [5]. Further, aspect ratio (AR), the ratio of the maximum diameter of the aneurysm to the width of the aneurysm neck, has been correlated with elevated risk of rupture [6]. The purpose of the current study is to explore the possibility of creating elastase induced aneurysms in rabbits with a range of aspect ratios (ratio of aneurysm height/neck) and evaluate the existence of a correlation between aspect ratio and WSS distribution. Aneurysms with ARs from 0.98 to 2.8 were created at the origin of the right common carotid artery (n = 30). Qualitative differences in WSS distribution were found in the high AR aneurysms (HARA) (AR>1.6) and low AR aneurysms (LARA) (AR<1.6) [7].


2018 ◽  
Vol 18 (05) ◽  
pp. 1850055
Author(s):  
ALFREDO ARANDA ◽  
ALVARO VALENCIA

CFD simulations were performed for 60 human cerebral aneurysms (30 previously ruptured and 30 previously unruptured) to study the behavior of the time-averaged wall shear stress (TAWSS) with respect to the aspect ratio (AR), implementing a set of low, normal, and high-pressure differences between the inlet and the outlets of each artery. It is well known that there exists a direct relationship between TAWSS and the rupture. In this investigation, we presented an important result because the condition of the pressure among the branches and the AR may be measured in any patient, then a slope may be associated, and finally a TAWSS may be estimated. We found that when the pressure difference increased, the absolute slopes between TAWSS and AR increased as well. Also, the magnitude of the slope in the previously unruptured aneurysms was 4.7 times the slope in the previously ruptured aneurysms. On the other hand, TAWSS was higher in the previously unruptured aneurysm than previously ruptured aneurysms due to the unruptured aneurysms that have a smaller surface area. Furthermore, we analyzed the relationship between TAWSS and other geometric parameters of the aneurysm, such as bottleneck and non-sphericity index; however, no correlation was found for either cases.


2013 ◽  
Vol 305 (8) ◽  
pp. C854-C866 ◽  
Author(s):  
Jennifer M. Dolan ◽  
Hui Meng ◽  
Fraser J. Sim ◽  
John Kolega

Flow impingement at arterial bifurcations causes high frictional force [or wall shear stress (WSS)], and flow acceleration and deceleration in the branches create positive and negative streamwise gradients in WSS (WSSG), respectively. Intracranial aneurysms tend to form in regions with high WSS and positive WSSG. However, little is known about the responses of endothelial cells (ECs) to either positive or negative WSSG under high WSS conditions. We used cDNA microarrays to profile gene expression in cultured ECs exposed to positive or negative WSSG for 24 h in a flow chamber where WSS varied between 3.5 and 28.4 Pa. Gene ontology and biological pathway analysis indicated that positive WSSG favored proliferation, apoptosis, and extracellular matrix processing while decreasing expression of proinflammatory genes. To determine if similar responses occur in vivo, we examined EC proliferation and expression of the matrix metalloproteinase ADAMTS1 under high WSS and WSSG created at the basilar terminus of rabbits after bilateral carotid ligation. Precise hemodynamic conditions were determined by computational fluid dynamic simulations from three-dimensional angiography and mapped on immunofluorescence staining for the proliferation marker Ki-67 and ADAMTS1. Both proliferation and ADAMTS1 were significantly higher in ECs under positive WSSG than in adjacent regions of negative WSSG. Our results indicate that WSSG elicits distinct EC gene expression profiles and particular biological pathways including increased cell proliferation and matrix processing. Such EC responses may be important in understanding the mechanisms of intracranial aneurysm initiation at regions of high WSS and positive WSSG.


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