scholarly journals Computing of Low Shear Stress-Driven Endothelial Gene Network Involved in Early Stages of Atherosclerotic Process

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Federico Vozzi ◽  
Jonica Campolo ◽  
Lorena Cozzi ◽  
Gianfranco Politano ◽  
Stefano Di Carlo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Transcription Factors ◽  
Gene Network ◽  
Bioinformatics Analysis ◽  
Atherosclerotic Disease ◽  
Cell Phenotype ◽  
Shear Stresses ◽  
Low Shear Stress ◽  
Low Shear

Background. In the pathogenesis of atherosclerosis, a central role is represented by endothelial inflammation with influx of chemokine-mediated leukocytes in the vascular wall. Aim of this study was to analyze the effect of different shear stresses on endothelial gene expression and compute gene network involved in atherosclerotic disease, in particular to homeostasis, inflammatory cell migration, and apoptotic processes.Methods. HUVECs were subjected to shear stress of 1, 5, and 10 dyne/cm2in a Flow Bioreactor for 24 hours to compare gene expression modulation. Total RNA was analyzed by Affymetrix technology and the expression of two specific genes (CXCR4 and ICAM-1) was validated by RT-PCR. To highlight possible regulations between genes and as further validation, a bioinformatics analysis was performed.Results. At low shear stress (1 dyne/cm2) we observed the following: (a) strong upregulation of CXCR4; (b) mild upregulation of Caspase-8; (c) mild downregulation of ICAM-1; (d) marked downexpression of TNFAIP3. Bioinformatics analysis showed the presence of network composed by 59 new interactors (14 transcription factors and 45 microRNAs) appearing strongly related to shear stress.Conclusions. The significant modulation of these genes at low shear stress and their close relationships through transcription factors and microRNAs suggest that all may promote an initial inflamed endothelial cell phenotype, favoring the atherosclerotic disease.

scholarly journals Bioinformatic identification of hub genes and related transcription factors in low shear stress treated endothelial cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yang Yang ◽  
Xiangshan Xu
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Cell Cycle ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Transcription Factors ◽  
Transcriptional Factor ◽  
Hub Genes ◽  
Low Shear Stress ◽  
Low Shear

Abstract Background Recent evidences indicated that shear stress is critical in orchestrating gene expression in cardiovascular disease. It is necessary to identify the mechanism of shear stress influencing gene expression in physiology and pathophysiology conditions. This paper aimed to identify candidate hub genes and its transcription factors with bioinformatics. Methods We analyzed microarray expression profile of GSE16706 to identify differentially expressed genes (DEGs) in low shear stress (1 dyne/cm2) treated human umbilical vein endothelial cells (HUVECs) compared with static condition for 24 h. Results 652 DEGs, including 333 up-regulated and 319 down-regulated DEGs, were screen out. Functional enrichment analysis indicated enrichment items mainly included cytokine-cytokine receptor interaction and cell cycle. Five hub genes (CDC20, CCNA2, KIF11, KIF2C and PLK1) and one significant module (score = 17.39) were identified through protein–protein interaction (PPI) analysis. Key transcriptional factor FOXC1 displayed close interaction with all the hub genes via gene-transcriptional factor network. Single-gene GSEA analysis indicated that CDC20 was linked to the G2M_CHECKPOINT pathway and cell cycle pathway. Conclusions By using integrated bioinformatic analysis, a new transcriptional factor and hub-genes network related to HUVECs treated with low shear stress were identified. The new regulation mechanism we discovered may be a promising potential therapeutic target for cardiovascular disease.

Plaque-prone hemodynamics impair endothelial function in pig carotid arteries

2006 ◽  
Vol 290 (6) ◽  
pp. H2320-H2328 ◽  
Author(s):  
Veronica Gambillara ◽  
Céline Chambaz ◽  
Gabriela Montorzi ◽  
Sylvain Roy ◽  
Nikos Stergiopulos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Oscillatory Shear ◽  
Enos Gene ◽  
Low Shear Stress ◽  
Oscillatory Shear Stress ◽  
Low Shear

Hemodynamic forces play an active role in vascular pathologies, particularly in relation to the localization of atherosclerotic lesions. It has been established that low shear stress combined with cyclic reversal of flow direction (oscillatory shear stress) affects the endothelial cells and may lead to an initiation of plaque development. The aim of the study was to analyze the effect of hemodynamic conditions in arterial segments perfused in vitro in the absence of other stimuli. Left common porcine carotid segments were mounted into an ex vivo arterial support system and perfused for 3 days under unidirectional high and low shear stress (6 ± 3 and 0.3 ± 0.1 dyn/cm2) and oscillatory shear stress (0.3 ± 3 dyn/cm2). Bradykinin-induced vasorelaxation was drastically decreased in arteries exposed to oscillatory shear stress compared with unidirectional shear stress. Impaired nitric oxide-mediated vasodilation was correlated to changes in both endothelial nitric oxide synthase (eNOS) gene expression and activation in response to bradykinin treatment. This study determined the flow-mediated effects on native tissue perfused with physiologically relevant flows and supports the hypothesis that oscillatory shear stress is a determinant factor in early stages of atherosclerosis. Indeed, oscillatory shear stress induces an endothelial dysfunction, whereas unidirectional shear stress preserves the function of endothelial cells. Endothelial dysfunction is directly mediated by a downregulation of eNOS gene expression and activation; consequently, a decrease of nitric oxide production and/or bioavailability occurs.

Activation of MAPK participates in low shear stress-induced IL-8 gene expression in endothelial cells

2008 ◽  
Vol 23 ◽  
pp. S96-S103 ◽  
Author(s):  
Min Cheng ◽  
Jiang Wu ◽  
Yi Li ◽  
Yongmei Nie ◽  
Huaiqing Chen
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Low Shear Stress ◽  
Low Shear

Analysis of Particle Trajectories in Aortic Artery Bifurcations With Stenosis

1989 ◽  
Vol 111 (4) ◽  
pp. 311-315 ◽  
Author(s):  
M. Nazemi ◽  
C. Kleinstreuer
Keyword(s):  
Shear Stress ◽  
Element Model ◽  
Spherical Particles ◽  
Shear Stresses ◽  
Atherosclerotic Lesions ◽  
Aortic Artery ◽  
Diseased Segment ◽  
Low Shear Stress ◽  
Accelerated Growth ◽  
Low Shear

The fluid-particle dynamics in a two-dimensonal symmetric branching channel with local occlusions representing a diseased segment of an aortic artery bifurcation has been analyzed. The validated finite element model simulates the trajectories and landing or impact sites of spherical particles for laminar flow in bifurcation channels with generalized wall conditions. Two hypotheses relating critical wall shear stress levels and plaque formation, previously postulated by Kleinstreuer et al. (1988) and Nazemi et al. (1989), have been confirmed. Low shear stress may contribute to the onset of atherosclerotic lesions and areas of critically low and high shear stresses are susceptible to accelerated growth of plaque.

Fluid Shear Stress Increases the Intra-cellular Storage Pool of Tissue-type Plasminogen Activator in Intact Human Conduit Vessels

2000 ◽  
Vol 84 (08) ◽  
pp. 291-298 ◽  
Author(s):  
Lena Sjögren ◽  
Liming Gan ◽  
Roya Doroudi ◽  
Christina Jern ◽  
Lennart Jungersten ◽  
...  
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Plasminogen Activator ◽  
Fluid Shear Stress ◽  
Mechanical Stimulus ◽  
Intraluminal Pressure ◽  
Tissue Type ◽  
Storage Pool ◽  
Low Shear Stress ◽  
Low Shear

SummaryWe investigated the effect of shear stress on the expression of tissuetype plasminogen activator (t-PA) in intact human conduit vessels. Human umbilical veins were exposed to high or low shear stress (25 vs < 4 dyn/cm2) at identical intraluminal pressure (20 mmHg) for 1.5, 3, and 6 h in a new computerized biomechanical perfusion system. High shear perfusion induced a marked, time-dependent increase in t-PA immunostaining in both the endothelium and the media. t-PA relative to GAPDH gene expression increased by 54 ± 14% in highcompared to low-sheared vessels (p = 0.002). By contrast, t-PA release into the perfusion medium was similar in vessels perfused under high or low shear stress conditions. The results show that shear stress independently of pressure is a potent fluid mechanical stimulus for upregulation of the intracellular storage pool of t-PA in the vascular wall of fresh human conduit vessels. The shear effect is associated with an increased t-PA gene expression.

Low shear stress-induced endothelial mesenchymal transformation via the down-regulation of TET2

2021 ◽  
Vol 545 ◽  
pp. 20-26
Author(s):  
AFang Li ◽  
LiLan Tan ◽  
ShuLei Zhang ◽  
Jun Tao ◽  
Zuo Wang ◽  
...  
Keyword(s):  
Shear Stress ◽  
Down Regulation ◽  
Low Shear Stress ◽  
Mesenchymal Transformation ◽  
Low Shear

Plaque and Shear Stress Distribution in Human Coronary Bifurcations: a Multi-Slice Computed Tomography Study

2007 ◽  
Author(s):  
Alina G. van der Giessen ◽  
Jolanda J. Wentzel ◽  
Frans N. van de Vosse ◽  
Antonius F. van der Steen ◽  
Pim J. de Feyter ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Shear Stress ◽  
Outer Wall ◽  
Atherosclerotic Plaques ◽  
Advanced Stage ◽  
Flow Divider ◽  
Low Shear Stress ◽  
Curved Vessels ◽  
Early Atherosclerosis ◽  
Low Shear

It is generally accepted that early atherosclerosis develops in low shear-stress (SS) regions such as the outer wall of arterial bifurcations and the inner bend of curved vessels (1). However, in clinical practice, it is common to observe atherosclerotic plaques at the flow-divider, or carina, of coronary bifurcations (2). Plaques at the carina are more frequently found in symptomatic patients, and may represent a more advanced stage of atherosclerosis. The carina is located in a region which is exposed to high SS. We hypothesize that if plaques are located in atheroprotective high SS regions, they have grown circumferentially from the atherogenic low SS regions.

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