scholarly journals Oscillatory shear stress promotes angiogenic effects in arteriovenous malformations endothelial cells

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jeong Yeop Ryu ◽  
Yun Hyun Kim ◽  
Joon Seok Lee ◽  
Jeong Woo Lee ◽  
Eun Jung Oh ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Shear Flow ◽  
Mechanical Stress ◽  
Vascular Endothelial Cells ◽  
Physiological Mechanism ◽  
Tissue Samples ◽  
Expression Levels ◽  
Before And After ◽  
Oscillatory Shear Stress

Abstract Background Vascular endothelial cells (ECs) are subject to continuous shear stress due to blood circulation. Mechanical stress due to high shear flow can also cause arteriovenous malformation (AVM) when ECs respond hyper-sensitively to shear flow. This study was conducted to test the hypothesis that angiogenesis could be promoted in response to mechanical stress via regulation of pro-angiogenic factors in AVM cells. Methods ECs were extracted from the tissue samples from six AVM patients and six normal patients. Shear stress at 7 dynes/cm2 were applied for 24 h. Before and after application of shear stress to each group, RT-PCR was performed to access the expression levels of angiopoietin2(AGP2), aquaporin1(AQP1) and TGFβR1. Immunofluorescences was also performed to evaluate the level of protein expressions. Results In both normal and AVM tissues, AGP2 and TGFβR1 under the shear stress showed increased expression in the ECs compared to the non-sheared samples. When AVMs and normal arterial vasculature were compared, the expression levels of both AGP2 and TGFβR1 in AVMs were higher when compared to normal arterial vasculature with or without shear stress. Immunofluorescence-based protein analysis also confirmed shear-induced AGP2 and TGFβR1 in both samples of normal and AVM patients. Conclusions AVMs exhibited higher sensitivity to shear stress by producing higher expressions of some marked genes and proteins that regulate the endothelial functions upon exposure to shear stress. While the physiological mechanism for AVMs remain elusive, our study shows the plausibility of physical stress imposed by the shearing flow can cause the occurrence of AVMs.

Tracings of Behavior of Myoblasts Cultured Under Couette Type of Shear Flow Between Parallel Disks

2021 ◽  
Author(s):  
Shigehiro Hashimoto ◽  
Hiroki Yonezawa
Keyword(s):  
Shear Stress ◽  
Shear Flow ◽  
Rotating Disk ◽  
Time Lapse ◽  
Mechanical Stimuli ◽  
Parallel Disks ◽  
Before And After ◽  
A Cell

Abstract A cell deforms and migrates on the scaffold under mechanical stimuli in vivo. In this study, a cell with division during shear stress stimulation has been observed in vitro. Before and after division, both migration and deformation of each cell were analyzed. To make a Couette-type shear flow, the medium was sandwiched between parallel disks (the lower stationary culture-disc and the upper rotating disk) with a constant gap. The wall shear stress (1.5 Pa < τ < 2 Pa) on the surface of the lower culture plate was controlled by the rotational speed of the upper disc. Myoblasts (C2C12: mouse myoblast cell line) were used in the test. After cultivation without flow for 24 hours for adhesion of the cells to the lower disk, constant τ was applied to the cells in the incubator for 7 days. The behavior of each cell during shear was tracked by time-lapse images observed by an inverted phase contrast microscope placed in the incubator. Experimental results show that each cell tends to divide after higher activities: deformation and migration. The tendency is remarkable at the shear stress of 1.5 Pa.

scholarly journals Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+ signaling in vascular endothelial cells

2018 ◽  
Vol 315 (5) ◽  
pp. H1477-H1485 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Hiromi Imamura ◽  
Joji Ando
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Vascular Endothelial Cells ◽  
Critical Role ◽  
Atp Release ◽  
Vascular Endothelial ◽  
The Novel ◽  
Caveolin 1 ◽  
Atp Generation

Vascular endothelial cells (ECs) sense and transduce hemodynamic shear stress into intracellular biochemical signals, and Ca2+ signaling plays a critical role in this mechanotransduction, i.e., ECs release ATP in the caveolae in response to shear stress and, in turn, the released ATP activates P2 purinoceptors, which results in an influx into the cells of extracellular Ca2+. However, the mechanism by which the shear stress evokes ATP release remains unclear. Here, we demonstrated that cellular mitochondria play a critical role in this process. Cultured human pulmonary artery ECs were exposed to controlled levels of shear stress in a flow-loading device, and changes in the mitochondrial ATP levels were examined by real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor. Immediately upon exposure of the cells to flow, mitochondrial ATP levels increased, which was both reversible and dependent on the intensity of shear stress. Inhibitors of the mitochondrial electron transport chain and ATP synthase as well as knockdown of caveolin-1, a major structural protein of the caveolae, abolished the shear stress-induced mitochondrial ATP generation, resulting in the loss of ATP release and influx of Ca2+ into the cells. These results suggest the novel role of mitochondria in transducing shear stress into ATP generation: ATP generation leads to ATP release in the caveolae, triggering purinergic Ca2+ signaling. Thus, exposure of ECs to shear stress seems to activate mitochondrial ATP generation through caveola- or caveolin-1-mediated mechanisms. NEW & NOTEWORTHY The mechanism of how vascular endothelial cells sense shear stress generated by blood flow and transduce it into functional responses remains unclear. Real-time imaging of mitochondrial ATP demonstrated the novel role of endothelial mitochondria as mechanosignaling organelles that are able to transduce shear stress into ATP generation, triggering ATP release and purinoceptor-mediated Ca2+ signaling within the cells.

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.

scholarly journals Low Shear Stress Upregulates CX3CR1 Expression by Inducing VCAM-1 via the NF-κB Pathway in Vascular Endothelial Cells

2020 ◽  
Vol 78 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Yiwei Zhao ◽  
Peile Ren ◽  
Qiufang Li ◽  
Shafiu Adam Umar ◽  
Tan Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Protein Expression ◽  
Vascular Endothelial Cells ◽  
Critical Role ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Low Shear Stress ◽  
Low Shear ◽  
Cx3cr1 Expression

Abstract Atherosclerosis is a significant cause of mortality and morbidity. Studies suggest that the chemokine receptor CX3CR1 plays a critical role in atherogenesis. Shear stress is an important mechanical force that affects blood vessel function. In this study, we investigated the effect of shear stress on CX3CR1 expression in vascular endothelial cells (VECs). First, cells were exposed to different shear stress and then CX3CR1 mRNA and protein were measured by quantitative RT-PCR and western blot analysis, respectively. CX3CR1 gene silencing was used to analyze the molecular mechanisms underlying shear stress-mediated effects on CX3CR1 expression. CX3CR1 mRNA and protein expression were significantly increased with 4.14 dyne/cm2 of shear stress compared with other tested levels of shear stress. We observed a significant increase in CX3CR1 mRNA levels at 2 h and CX3CR1 protein expression at 4 h. CX3CR1-induced VCAM-1 expression in response to low shear stress by activating NF-κB signaling pathway in VECs. Our findings demonstrate that low shear stress increases CX3CR1 expression, which increases VCAM-1 expression due to elevated NF-κB activation. The current study provides evidence of the correlation between shear stress and atherosclerosis mediated by CX3CR1.

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

scholarly journals Deep transcriptomic profiling reveals the similarity between endothelial cells cultured under static and oscillatory shear stress conditions

2016 ◽  
Vol 48 (9) ◽  
pp. 660-666 ◽  
Author(s):  
Congzhen Qiao ◽  
Fan Meng ◽  
Inhwan Jang ◽  
Hanjoong Jo ◽  
Y. Eugene Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Function ◽  
Stress Conditions ◽  
Individual Gene ◽  
Gene Level ◽  
The Individual ◽  
Oscillatory Shear Stress ◽  
Whole Transcriptome ◽  
Transcriptome Level

Atherosclerosis is a multifactorial disease that preferentially develops in specific regions in the arterial tree. This characteristic is mainly attributed to the unique pattern of hemodynamic shear stress in vivo. High laminar shear stress (LS) found in straight lumen exerts athero-protective effects. Low or oscillatory shear stress (OS) present in regions of lesser curvature and arterial bifurcations predisposes arterial intima to atherosclerosis. Shear stress-regulated endothelial function plays an important role in the process of atherosclerosis. Most in vitro research studies focusing on the molecular mechanisms of endothelial function are performed in endothelial cells (ECs) under cultured static (ST) condition. Some findings, however, are not recapitulated in subsequent translational studies, mostly likely due to the missing biomechanical milieu. Here, we profiled the whole transcriptome of primary human coronary arterial endothelial cells (HCAECs) under different shear stress conditions with RNA sequencing. Among 16,313 well-expressed genes, we detected 8,177 that were differentially expressed in OS vs. LS conditions and 9,369 in ST vs. LS conditions. Notably, only 1,618 were differentially expressed in OS vs. ST conditions. Hierarchical clustering of ECs demonstrated a strong similarity between ECs under OS and ST conditions at the transcriptome level. Subsequent pairwise heat mapping and principal component analysis gave further weight to the similarity. At the individual gene level, expressional analysis of representative well-known genes as well as novel genes showed a comparable amount at mRNA and protein levels in ECs under ST and OS conditions. In conclusion, the present work compared the whole transcriptome of HCAECs under different shear stress conditions at the transcriptome level as well as at the individual gene level. We found that cultured ECs are significantly different from those under LS conditions. Thus using cells under ST conditions is unlikely to elucidate endothelial physiology. Given the revealed high similarities of the endothelial transcriptome under OS and ST conditions, it may be helpful to understand the underlying mechanisms of OS-induced endothelial dysfunction from static cultured endothelial studies.

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