scholarly journals Low shear stress up-regulation of proinflammatory gene expression in human retinal microvascular endothelial cells

2013 ◽  
Vol 116 ◽  
pp. 308-311 ◽  
Author(s):  
Akihiro Ishibazawa ◽  
Taiji Nagaoka ◽  
Harumasa Yokota ◽  
Shinji Ono ◽  
Akitoshi Yoshida
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Microvascular Endothelial Cells ◽  
Low Shear Stress ◽  
Proinflammatory Gene ◽  
Microvascular Endothelial ◽  
Proinflammatory Gene Expression ◽  
Low Shear

Prolonged shear stress and KLF2 suppress constitutive proinflammatory transcription through inhibition of ATF2

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4249-4257 ◽  
Author(s):  
Joost O. Fledderus ◽  
Johannes V. van Thienen ◽  
Reinier A. Boon ◽  
Rob J. Dekker ◽  
Jakub Rohlena ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Umbilical Vein ◽  
Expression Profiles ◽  
Binding Activity ◽  
Tnf Α ◽  
Proinflammatory Gene ◽  
Umbilical Vein Endothelial Cells ◽  
Proinflammatory Gene Expression

Abstract Absence of shear stress due to disturbed blood flow at arterial bifurcations and curvatures leads to endothelial dysfunction and proinflammatory gene expression, ultimately resulting in atherogenesis. KLF2 has recently been implicated as a transcription factor involved in mediating the anti-inflammatory effects of flow. We investigated the effect of shear on basal and TNF-α–induced genomewide expression profiles of human umbilical vein endothelial cells (HUVECs). Cluster analysis confirmed that shear stress induces expression of protective genes including KLF2, eNOS, and thrombomodulin, whereas basal expression of TNF-α–responsive genes was moderately decreased. Promoter analysis of these genes showed enrichment of binding sites for ATF transcription factors, whereas TNF-α–induced gene expression was mostly NF-κB dependent. Furthermore, human endothelial cells overlying atherosclerotic plaques had increased amounts of phosphorylated nuclear ATF2 compared with endothelium at unaffected sites. In HUVECs, a dramatic reduction of nuclear binding activity of ATF2 was observed under shear and appeared to be KLF2 dependent. Reduction of ATF2 with siRNA potently suppressed basal proinflammatory gene expression under no-flow conditions. In conclusion, we demonstrate that shear stress and KLF2 inhibit nuclear activity of ATF2, providing a potential mechanism by which endothelial cells exposed to laminar flow are protected from basal proinflammatory, atherogenic gene expression.

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

Gene expression profiles of glucose toxicity-exposed islet microvascular endothelial cells

2018 ◽  
Vol 25 (4) ◽  
pp. e12450 ◽  
Author(s):  
Mingming Liu ◽  
Wenbao Lu ◽  
Qunxing Hou ◽  
Bing Wang ◽  
Youming Sheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Microvascular Endothelial Cells ◽  
Glucose Toxicity ◽  
Microvascular Endothelial

scholarly journals MicroRNA-Regulated Rickettsial Invasion into Host Endothelium via Fibroblast Growth Factor 2 and Its Receptor FGFR1

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 240 ◽  
Author(s):  
Abha Sahni ◽  
Hema Narra ◽  
Jignesh Patel ◽  
Sanjeev Sahni
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Host Cells ◽  
Microvascular Endothelial Cells ◽  
Target Cells ◽  
Fibroblast Growth ◽  
Wide Range ◽  
Microvascular Endothelial

Microvascular endothelial cells (ECs) represent the primary target cells during human rickettsioses and respond to infection via the activation of immediate–early signaling cascades and the resultant induction of gene expression. As small noncoding RNAs dispersed throughout the genome, microRNAs (miRNAs) regulate gene expression post-transcriptionally to govern a wide range of biological processes. Based on our recent findings demonstrating the involvement of fibroblast growth factor receptor 1 (FGFR1) in facilitating rickettsial invasion into host cells and published reports suggesting miR-424 and miR-503 as regulators of FGF2/FGFR1, we measured the expression of miR-424 and miR-503 during R. conorii infection of human dermal microvascular endothelial cells (HMECs). Our results revealed a significant decrease in miR-424 and miR-503 expression in apparent correlation with increased expression of FGF2 and FGFR1. Considering the established phenomenon of endothelial heterogeneity and pulmonary and cerebral edema as the prominent pathogenic features of rickettsial infections, and significant pathogen burden in the lungs and brain in established mouse models of disease, we next quantified miR-424 and miR-503 expression in pulmonary and cerebral microvascular ECs. Again, R. conorii infection dramatically downregulated both miRNAs in these tissue-specific ECs as early as 30 min post-infection in correlation with higher FGF2/FGFR1 expression. Changes in the expression of both miRNAs and FGF2/FGFR1 were next confirmed in a mouse model of R. conorii infection. Furthermore, miR-424 overexpression via transfection of a mimic into host ECs reduced the expression of FGF2/FGFR1 and gave a corresponding decrease in R. conorii invasion, while an inhibitor of miR-424 had the expected opposite effect. Together, these findings implicate the rickettsial manipulation of host gene expression via regulatory miRNAs to ensure efficient cellular entry as the critical requirement to establish intracellular infection.

W1594 Importins α1 and α3 Regulate VEGF Gene Expression and Angiogenesis in Gastric Mucosal Microvascular Endothelial Cells.

2009 ◽  
Vol 136 (5) ◽  
pp. A-698-A-699
Author(s):  
Amrita Ahluwalia ◽  
Xiaoming Deng ◽  
Vipal Gandhi ◽  
Sushrut S. Thiruvengadam ◽  
Andrzej S. Tarnawski
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Microvascular Endothelial Cells ◽  
Vegf Gene ◽  
Microvascular Endothelial

scholarly journals Effects of Caveolin-1-ERK1/2 pathway on endothelial cells and smooth muscle cells under shear stress

2019 ◽  
Vol 245 (1) ◽  
pp. 21-33 ◽  
Author(s):  
Lan Jia ◽  
Lihua Wang ◽  
Fang Wei ◽  
Chen Li ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Caveolin 1 ◽  
Low Shear Stress ◽  
And Migration ◽  
Oscillating Shear Stress ◽  
Low Shear ◽  
Proliferation And Migration

Hemodynamic forces have an important role in venous intimal hyperplasia, which is the main cause of arteriovenous fistula dysfunction. Endothelial cells (ECs) constantly exposed to the shear stress of blood flow, converted the mechanical stimuli into intracellular signals, and interacted with the underlying vascular smooth muscle cells (VSMCs). Caveolin-1 is one of the important mechanoreceptors on cytomembrane, which is related to vascular abnormalities. Extracellular signal-regulated kinase1/2 (ERK1/2) pathway is involved in the process of VSMCs proliferation and migration. In the present study, we explore the effects of Caveolin-1-ERK1/2 pathway and uremia toxins on the endothelial cells and VSMCs following shear stress application. Different shear stress was simulated with a ECs/VSMCs cocultured parallel-plate flow chamber system. Low shear stress and oscillating shear stress up-regulated the expression of fibroblast growth factor-4, platelet-derived growth factor-BB, vascular endothelial growth factor-A, ERK1/2 phosphorylation in endothelial cells, and proliferation and migration of VSMCs but down-regulated the Caveolin-1 expression in endothelial cells. Uremia toxin induces the proliferation and migration of VSMCs but not in a Caveolin-1-dependent manner in the static environment. Low shear stress-induced proliferation and migration of VSMCs is inhibited by Caveolin-1 overexpression and ERK1/2 suppression. Shear stress-regulated VSMC proliferation and migration is an endothelial cells-dependent process. Low shear stress and oscillating shear stress exert atherosclerotic influences on endothelial cells and VSMCs. Low shear stress modulated proliferation and migration of VSMCs through Caveolin-1-ERK1/2 pathway, which suggested that Caveolin-1 and ERK1/2 can be used as a new therapeutic target for the treatment of arteriovenous fistula dysfunction. Impact statement Venous intimal hyperplasia is the leading cause of arteriovenous fistula (AVF) dysfunction. This article reports that shear stress-regulated vascular smooth muscle cells (VSMCs) proliferation and migration is an endothelial cell (EC)-dependent process. Low shear stress (LSS) and oscillating shear stress (OSS) exert atherosclerotic influences on the ECs and VSMCs. LSS-induced proliferation and migration of VSMCs is inhibited by Caveolin-1 overexpression and extracellular signal-regulated kinase1/2 (ERK1/2) suppression, which suggested that Caveolin-1 and ERK1/2 can be used as a new therapeutic target for the treatment of AVF dysfunction.

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