scholarly journals Monocyte recruitment to endothelial cells in response to oscillatory shear stress

2003 ◽  
Vol 17 (12) ◽  
pp. 1648-1657 ◽  
Author(s):  
Tzung K. Hsiai ◽  
Sung K. Cho ◽  
Pak K. Wong ◽  
Mike Ing ◽  
Adler Salazar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Oscillatory Shear ◽  
Monocyte Recruitment ◽  
Oscillatory Shear Stress

Abstract 363: Lim Domain Only 4 Is a Shear-Sensitive Protein, Playing a Critical Role in Endothelial Inflammation and Atherosclerosis

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Wakako Takabe ◽  
Chih-Wen Ni ◽  
Dong Ju Son ◽  
Noah Alberts-Grill ◽  
Hanjoong Jo
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Critical Role ◽  
Oscillatory Shear ◽  
Lim Domain ◽  
Disturbed Flow ◽  
Endothelial Inflammation ◽  
And Migration ◽  
Oscillatory Shear Stress ◽  
Stable Flow

Recently, we have shown that disturbed flow, characterized by low and oscillatory shear stress, caused by a partial ligation of mouse left carotid artery (LCA) rapidly induces atherosclerosis. Using the partial ligation model and genome-wide microarray study with aortic endothelial RNAs obtained directly from the flow-disturbed carotid arteries, we previously identified mechanosensitive genes in mouse endothelial RNA including LIM domain only 4 ( lmo4 ). Here we report that LMO4 is a shear-sensitive protein that regulates endothelial inflammation. Lmo4 was up-regulated by disturbed flow in mouse LCA compared to the contralateral right CA (RCA) exposed to stable flow. At protein levels, LMO4 expression was significantly higher not only in LCA in our surgical model but also in the lesser curvature (flow-disturbed and athero-prone region of mouse aortic arch) compared to the greater curvature (stable-flow and ather-protected region). In addition, immunohistochemical staining of LMO4 in human coronary arteries revealed that its expression is detectable only in intimal endothelial cells, but not in medial cells. While LMO4 is known as a potential oncogene and associated with growth, migration and invasion of breast cancer cells, its role in cardiovascular system is not known to our knowledge. We tested a hypothesis that LMO4 is a mechanosensitive gene and plays a critical role in regulation of endothelial cell biology. LMO4 protein expression was robustly induced by oscillatory shear stress (OS) compared to laminar shear (LS) in human umbilical vein endothelial cells (HUVEC). Treatment of HUVEC with siRNA against LMO4 significantly inhibited OS-induced inflammation and migration, but not apoptosis and cell cycle progression. Further, LMO4 siRNA treatment significantly blunted expression of VCAM-1 and interleukin-8 induced by OS in endothelial cells. These results suggest that LMO4 is a shear-induced gene that plays a critical role in OS-induced endothelial inflammation and migration, and potentially in atherosclerosis.

Integrated microfluidic chip for endothelial cells culture and analysis exposed to a pulsatile and oscillatory shear stress

Lab on a Chip ◽  
2009 ◽  
Vol 9 (21) ◽  
pp. 3118 ◽  
Author(s):  
Jianbo Shao ◽  
Lei Wu ◽  
Jianzhang Wu ◽  
Yunhuan Zheng ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Microfluidic Chip ◽  
Oscillatory Shear ◽  
Oscillatory Shear Stress

Non-Invasive Molecular Imaging of Shear Stress-Induced Endothelial Activation and Atherosclerotic Plaque Vulnerability

2012 ◽  
Author(s):  
K. Van der Heiden ◽  
H. C. Groen ◽  
P. C. Evans ◽  
L. Speelman ◽  
F. Gijsen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Atherosclerotic Lesion ◽  
Oscillatory Shear ◽  
Lesion Development ◽  
Non Invasive ◽  
Oscillatory Shear Stress ◽  
The Relationship ◽  
Atherosclerotic Lesion Development

Atherosclerosis is a lipid- and inflammation driven disease of the larger arteries and is found at specific locations in the arterial tree, i.e. at branches and bends where endothelial cells are exposed to low and low, oscillatory shear stress. Shear stress, the frictional force acting on the endothelial cells as a result of the blood flow, affects endothelial physiology. It determines the location of atherosclerotic lesion development as low and low, oscillatory shear stress induce pro-inflammatory transcription factors but reduce expression and/or activity of anti-inflammatory transcription factors in endothelial cells, rendering the vascular wall vulnerable for inflammation. Consequently, in the presence of atherosclerotic risk factors, such as hypercholesterolemia and diabetes, atherosclerotic lesion development can occur. Although the relationship between low and low, oscillatory shear stress and the prevalence of atherosclerosis has been recognized for several decades, insight into the mechanisms underlying this relationship is still incomplete. The correlation between shear stress and endothelial inflammation was demonstrated by in vitro experiments, in which cultured endothelial cells were exposed to specific flow profiles, and confirmed in vivo by gene expression pattern studies at atherosclerosis-susceptible sites. However, the relationship was not substantiated by direct causal in vivo evidence. Therefore, we developed a method to change the local shear stress field in mice in vivo and studied its effect on the endothelial molecular pathways and resulting atherosclerotic plaque formation. Moreover it allowed us to develop non-invasive molecular imaging strategies to detect vulnerable plaques.

Tissue Factor Activity Is Upregulated in Human Endothelial Cells Exposed to Oscillatory Shear Stress

2002 ◽  
Vol 87 (06) ◽  
pp. 1062-1068 ◽  
Author(s):  
Paolo Silacci ◽  
Karima Bouzourene ◽  
François Daniel ◽  
Hans Brunner ◽  
Daniel Hayoz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Protein Expression ◽  
Tissue Factor ◽  
Critical Role ◽  
Oscillatory Shear ◽  
Human Endothelial Cells ◽  
Static Conditions ◽  
Oscillatory Shear Stress

SummaryHemodynamic forces play a critical role in the pathogenesis of atherosclerosis as evidenced by the focal nature of the disease. Oscillatory shear stress characterizes the hemodynamic environment of plaque-prone areas as opposed to unidirectional shear stress typical of plaque-free areas. These particular flow conditions modulate atherosclerosis-related genes. Tissue factor (TF) initiates blood coagulation, contributes to vascular remodeling, and is therefore a potential contributor in the development/progression of atherosclerosis. We investigated the effect of oscillatory and unidirectional flows on TF using an in vitro perfusion system. Human endothelial cells exposed for 24 h to oscillatory shear stress, significantly increased TF mRNA, and TF protein expression (1.5-and 1.75-fold, respectively, p <0.01), and surface TF activity (twofolds-increase). Expression of TF inhibitor (TFPI), mRNA and protein, remained unchanged as compared to static conditions. Conversely, cells exposed to unidirectional shear, showed a decrease in TF activity with a significant increase in TFPI mRNA and protein expression (1.5-and 1.8-fold, respectively, p <0.01). These results show for the first time that pulsatile oscillatory shear stress induces a procoagulant phenotype of endothelial cells which may favor formation/progression of atherothrombotic lesions.

A Novel Role of Id1 in Regulating Oscillatory Shear Stress-Mediated Lipid Uptake in Endothelial Cells

2018 ◽  
Vol 46 (6) ◽  
pp. 849-863 ◽  
Author(s):  
Kang Zhang ◽  
Yidan Chen ◽  
Tian Zhang ◽  
Lu Huang ◽  
Yi Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Oscillatory Shear ◽  
Lipid Uptake ◽  
Oscillatory Shear Stress

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.

scholarly journals Oscillatory Shear Stress Induces Oxidative Stress via TLR4 Activation in Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zhimei Wang ◽  
Feng Wang ◽  
Xiangquan Kong ◽  
Xiaofei Gao ◽  
Yue Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Flow Chamber ◽  
Oscillatory Shear ◽  
Tlr4 Activation ◽  
Oscillatory Shear Stress ◽  
Endothelial Homeostasis ◽  
Endothelial Nitric Oxide

Background. Oscillatory shear stress (OSS) disrupts endothelial homeostasis and promotes oxidative stress, which can lead to atherosclerosis. In atherosclerotic lesions, Toll-like receptor 4 (TLR4) is highly expressed. However, the molecular mechanism by which TLR4 modulates oxidative changes and the cell signaling transudation upon OSS is yet to be determined. Methods and Results. Carotid artery constriction (CAC) surgery and a parallel-plate flow chamber were used to modulate shear stress. The results showed that OSS significantly increased the oxidative burden, and this was partly due to TLR4 activation. OSS activated NOX2 and had no significant influence to NOX1 or NOX4 in endothelial cells (ECs). OSS phosphorylated caveolin-1, promoted its binding with endothelial nitric oxide synthase (eNOS), and resulted in deactivation of eNOS. TLR4 inhibition restored levels of nitric oxide (NO) and superoxide dismutase (SOD) in OSS-exposed cells. Conclusion. TLR4 modulates OSS-induced oxidative stress by activating NOX2 and suppressing eNOS.

scholarly journals MicroRNA-663 upregulated by oscillatory shear stress plays a role in inflammatory response of endothelial cells

2011 ◽  
Vol 300 (5) ◽  
pp. H1762-H1769 ◽  
Author(s):  
Chih-Wen Ni ◽  
Haiwei Qiu ◽  
Hanjoong Jo
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Inflammatory Response ◽  
Nucleic Acids ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Oscillatory Shear ◽  
Monocyte Adhesion ◽  
Locked Nucleic Acids ◽  
Oscillatory Shear Stress

The mechanisms by which oscillatory shear stress (OS) induces, while high laminar shear stress (LS) prevents, atherosclerosis are still unclear. Here, we examined the hypothesis that OS induces inflammatory response, a critical atherogenic event, in endothelial cells by a microRNA (miRNA)-dependent mechanism. By miRNA microarray analysis using total RNA from human umbilical vein endothelial cells (HUVECs) that were exposed to OS or LS for 24 h, we identified 21 miRNAs that were differentially expressed. Of the 21 miRNAs, 13 were further examined by quantitative PCR, which validated the result for 10 miRNAs. Treatment of HUVECs with the miR-663 antagonist (miR-663-locked nucleic acids) blocked OS-induced monocyte adhesion, but not apoptosis. In contrast, overexpression of miR-663 increased monocyte adhesion in LS-exposed cells. Subsequent mRNA expression microarray study using HUVECs treated with miR-663-locked nucleic acids and OS revealed 32 up- and 3 downregulated genes, 6 of which are known to be involved in inflammatory response. In summary, we identified 10 OS-sensitive miRNAs, including miR-663, which plays a key role in OS-induced inflammatory responses by mediating the expression of inflammatory gene network in HUVECs. These OS-sensitive miRNAs may mediate atherosclerosis induced by disturbed flow.

Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress

2003 ◽  
Vol 285 (6) ◽  
pp. H2290-H2297 ◽  
Author(s):  
J. Scott McNally ◽  
Michael E. Davis ◽  
Don P. Giddens ◽  
Aniket Saha ◽  
Jinah Hwang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Oscillatory Shear ◽  
Oxygen Species ◽  
Aortic Endothelial Cells ◽  
Protein Levels ◽  
Text Production ◽  
Bovine Aortic Endothelial Cells ◽  
Oscillatory Shear Stress

Oscillatory shear stress occurs at sites of the circulation that are vulnerable to atherosclerosis. Because oxidative stress contributes to atherosclerosis, we sought to determine whether oscillatory shear stress increases endothelial production of reactive oxygen species and to define the enzymes responsible for this phenomenon. Bovine aortic endothelial cells were exposed to static, laminar (15 dyn/cm2), and oscillatory shear stress (±15 dyn/cm2). Oscillatory shear increased superoxide ([Formula: see text]) production by more than threefold over static and laminar conditions as detected using electron spin resonance (ESR). This increase in [Formula: see text] was inhibited by oxypurinol and culture of endothelial cells with tungsten but not by inhibitors of other enzymatic sources. Oxypurinol also prevented H2O2 production in response to oscillatory shear stress as measured by dichlorofluorescin diacetate and Amplex Red fluorescence. Xanthine-dependent [Formula: see text] production was increased in homogenates of endothelial cells exposed to oscillatory shear stress. This was associated with decreased xanthine dehydrogenase (XDH) protein levels and enzymatic activity resulting in an elevated ratio of xanthine oxidase (XO) to XDH. We also studied endothelial cells lacking the p47 phox subunit of the NAD(P)H oxidase. These cells exhibited dramatically depressed [Formula: see text] production and had minimal XO protein and activity. Transfection of these cells with p47 phox restored XO protein levels. Finally, in bovine aortic endothelial cells, prolonged inhibition of the NAD(P)H oxidase with apocynin decreased XO protein levels and prevented endothelial cell stimulation of [Formula: see text] production in response to oscillatory shear stress. These data suggest that the NAD(P)H oxidase maintains endothelial cell XO levels and that XO is responsible for increased reactive oxygen species production in response to oscillatory shear stress.

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