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 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.

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

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 Paracrine Shear-Stress-Dependent Signaling from Endothelial Cells Affects Downstream Endothelial Function and Inflammation

2021 ◽  
Vol 22 (24) ◽  
pp. 13300
Author(s):  
Fabio Bertani ◽  
Dalila Di Francesco ◽  
Maria Dolores Corrado ◽  
Maria Talmon ◽  
Luigia Grazia Fresu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Conditioned Media ◽  
Coronary Microvascular Dysfunction ◽  
Experimental Conditions ◽  
Low Shear Stress ◽  
Stress Dependent ◽  
Low Shear

Cardiovascular diseases (CVDs), mainly ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and major contributors to disability worldwide. Despite their heterogeneity, almost all CVDs share a common feature: the endothelial dysfunction. This is defined as a loss of functionality in terms of anti-inflammatory, anti-thrombotic and vasodilatory abilities of endothelial cells (ECs). Endothelial function is greatly ensured by the mechanotransduction of shear forces, namely, endothelial wall shear stress (WSS). Low WSS is associated with endothelial dysfunction, representing the primary cause of atherosclerotic plaque formation and an important factor in plaque progression and remodeling. In this work, the role of factors released by ECs subjected to different magnitudes of shear stress driving the functionality of downstream endothelium has been evaluated. By means of a microfluidic system, HUVEC monolayers have been subjected to shear stress and the conditioned media collected to be used for the subsequent static culture. The results demonstrate that conditioned media retrieved from low shear stress experimental conditions (LSS-CM) induce the downregulation of endothelial nitric oxide synthase (eNOS) expression while upregulating peripheral blood mononuclear cell (PBMC) adhesion by means of higher levels of adhesion molecules such as E-selectin and ICAM-1. Moreover, LSS-CM demonstrated a significant angiogenic ability comparable to the inflammatory control media (TNFα-CM); thus, it is likely related to tissue suffering. We can therefore suggest that ECs stimulated at low shear stress (LSS) magnitudes are possibly involved in the paracrine induction of peripheral endothelial dysfunction, opening interesting insights into the pathogenetic mechanisms of coronary microvascular dysfunction.

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.

Juglanin suppresses oscillatory shear stress-induced endothelial dysfunction: An implication in atherosclerosis

2020 ◽  
Vol 89 ◽  
pp. 107048
Author(s):  
Jian Zhao ◽  
Xiaoqiang Quan ◽  
Zhouliang Xie ◽  
Leilei Zhang ◽  
Zhiwei Ding
Keyword(s):  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Oscillatory Shear ◽  
Oscillatory Shear Stress

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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