Does habitual endurance exercise protect endothelial function against acute exposure to oscillatory shear stress?

2019 ◽  
Author(s):  
A. S. Grewal ◽  
J. C. Tremblay ◽  
N. Preobrazenski ◽  
B. J. Gurd
Keyword(s):  
Physical Activity ◽  
Shear Stress ◽  
Endothelial Function ◽  
Endurance Exercise ◽  
Lower Limb ◽  
Rest Period ◽  
Oscillatory Shear ◽  
Acute Exposure ◽  
Before And After ◽  
Oscillatory Shear Stress

Introduction: Acute exposure to increases in oscillatory shear stress (increased retrograde shear stress and decreased mean shear stress) reduces flow-mediated dilation (FMD). This impairment may be mediated via increased oxidative stress. Habitual endurance exercise training results in increased antioxidant protection. However, it is currently unknown whether these adaptations protect against oscillatory shear stress-induced impairments in FMD. Purpose and Hypothesis: The purpose of this study is to determine whether lower limb endurance-trained athletes have protection against oscillatory shear stress-induced impairments in FMD compared to sedentary individuals. It is hypothesized that athletes will have a preserved FMD after an acute oscillatory shear stress intervention, compared to their sedentary counterparts. Methods: Healthy, young adult volunteers (18-29 years old) will be screened for physical activity (PA) through a physical activity recall questionnaire. 12 sedentary individuals (<3h of structured PA/week) and 12 lower limb endurance athletes will be recruited to participate.  All participants will complete a VO2 peak test to objectively measure cardiorespiratory fitness. Participants will visit the laboratory twice in the same week for vascular testing. Both 90-minute visits will begin with 45 minutes of supine rest, followed by a brachial artery FMD test before and after 30 minutes of either imposed oscillatory shear stress (forearm cuff inflated to 70 mmHg) or a 30 min rest period (control).  Significance: This will be the first study to investigate whether endurance-trained athletes are resistant to oscillatory shear-stress induced impairments in endothelial function. This will provide insight into mechanism contributing to the vasoprotective effects of habitual endurance exercise.

scholarly journals Evidence of sex differences in the acute impact of oscillatory shear stress on endothelial function

2019 ◽  
Vol 126 (2) ◽  
pp. 314-321 ◽  
Author(s):  
Joshua C. Tremblay ◽  
Taylor V. Stimpson ◽  
Kyra E. Pyke
Keyword(s):  
Shear Stress ◽  
Sex Differences ◽  
Shear Rate ◽  
Endothelial Function ◽  
Oscillatory Shear ◽  
Flow Mediated Dilation ◽  
Similar Stimulus ◽  
Men And Women ◽  
Oscillatory Shear Stress ◽  
The Impact

Acutely imposed oscillatory shear stress (OSS) reduces reactive hyperemia flow-mediated dilation (RH-FMD) in conduit arteries of men; however, whether a similar impairment occurs in women or with FMD in response to a controlled, sustained shear stress stimulus (SS-FMD) is unknown. The purpose of this study was to determine the impact of OSS on RH-FMD and SS-FMD in men and women. OSS was provoked in the brachial artery using a 30-min forearm cuff inflation (70 mmHg). Healthy men [ n = 16, 25 yr (SD 3)] and women [ n = 16, 21 yr (SD 2)] completed the OSS intervention twice (separate days). Brachial artery endothelial function was assessed pre- and postintervention via either RH-FMD or 6 min of handgrip SS-FMD using Duplex ultrasound. The RH-FMD stimulus was calculated as shear rate area under the curve 60 s postdeflation (SRAUC60), whereas SS-FMD shear rate was targeted to produce a similar stimulus pre- and postintervention. The OSS intervention decreased RH-FMD in both sexes [men: 6.2% (SD 3.4) to 5.2% (SD 3.0); women: 5.4% (SD 2.0) to 3.1% (SD 1.8), P < 0.001), although this was accompanied by a reduced SRAUC60. There was no significant effect of the intervention on RH-FMD with SRAUC60 as a covariate ( P = 0.310). Handgrip exercise elicited a similar stimulus before and after the intervention ( P = 0.287) in men and women ( P = 0.873). Men demonstrated blunted SS-FMD [4.8% (SD 1.9) to 3.2% (SD 1.9), P < 0.001], whereas women displayed preserved SS-FMD following the intervention [3.5% (SD 1.9) to 4.0% (SD 1.9), P = 0.061]. The lower SS-FMD in men but not women following OSS provides evidence of sex differences in the effects of OSS on conduit artery endothelial function. NEW & NOTEWORTHY Acute exposure to oscillatory shear stress induces transient endothelial dysfunction in men; however, whether women experience similar impairments is unknown. Following acutely imposed oscillatory shear stress, there was a decrease in flow-mediated dilation stimulated by a physiologically relevant sustained increase in shear stress in men but not in premenopausal women. These findings demonstrate, for the first time in humans that there are sex differences in the impact of oscillatory shear stress on endothelial function.

scholarly journals UBC-Nepal Expedition: imposed oscillatory shear stress does not further attenuate flow-mediated dilation during acute and sustained hypoxia

2018 ◽  
Vol 315 (1) ◽  
pp. H122-H131 ◽  
Author(s):  
Joshua C. Tremblay ◽  
Connor A. Howe ◽  
Philip N. Ainslie ◽  
Kyra E. Pyke
Keyword(s):  
Shear Stress ◽  
Endothelial Function ◽  
Acute Hypoxia ◽  
Reactive Hyperemia ◽  
Duplex Ultrasound ◽  
Oscillatory Shear ◽  
Flow Mediated Dilation ◽  
Oscillatory Shear Stress ◽  
Sustained Hypoxia ◽  
Experimentally Induced

Experimentally induced oscillatory shear stress (OSS) and hypoxia reduce endothelial function in humans. Acute and sustained hypoxia may cause increases in resting OSS; however, whether this influences endothelial susceptibility to further increases in OSS is unknown. Healthy lowlanders ( n = 15, 30 ± 6 yr; means ± SD) participated in three OSS interventions: two interventions at sea level [normoxia and after 20 min of normobaric hypoxia (acute hypoxia, 11% O2)] and one intervention 5–7 days after a 9-day ascent to 5,050 m (sustained hypoxia). OSS was provoked in the brachial artery using a 30-min distal cuff inflation (75 mmHg). Endothelial function was assessed before and after each intervention by reactive hyperemia flow-mediated dilation (FMD). Shear stress magnitude and patterns were obtained via Duplex ultrasound. Baseline retrograde shear stress and OSS were greater in acute hypoxia versus normoxia ( P < 0.001), and OSS was elevated in sustained hypoxia versus normoxia ( P = 0.011). The intervention further augmented OSS during each condition. Preintervention FMD was decreased by 29 ± 48% in acute hypoxia and by 25 ± 31% in sustained hypoxia compared with normoxia ( P = 0.001 and 0.026); these changes correlated with changes in baseline mean and antegrade shear stress. After the intervention, FMD decreased during normoxia (−41 ± 26%, P < 0.001) and was unaltered during acute or sustained hypoxia. Therefore, a 30-min exposure to OSS reduced FMD during normoxia, a condition with an unchallenged, healthy endothelium; however, imposed OSS did not appear to worsen endothelial function during acute or sustained hypoxia. Exposure to an altered magnitude and pattern of shear stress at baseline in hypoxia may contribute to the insensitivity to further acute augmentation of OSS. NEW & NOTEWORTHY We investigated whether the endothelium remains sensitive to experimental increases in oscillatory shear stress in acute (11% O2) and sustained (2 wk at 5,050 m) hypoxia. Hypoxia altered baseline shear stress and decreased endothelial function (flow-mediated dilation); however, exposure to experimentally induced oscillatory shear stress only impaired flow-mediated dilation in normoxia.

Abstract 561: Dysregulation of miR-155 in Acute Oscillatory Shear Stress (OSS)-mediated Oxidative Stress, Inflammation and Endothelial Dysfunction

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Islam Mohamed ◽  
Sheena Thomas ◽  
Kimberly Rooney ◽  
Roy Sutliff ◽  
Nick Willett ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Shear Stress ◽  
Barrier Function ◽  
Oscillatory Shear ◽  
Blue Dye ◽  
Down Regulation ◽  
Inflammatory Stress ◽  
Cytoskeleton Organization ◽  
Oscillatory Shear Stress

Introduction: Shear stress forces play an integral role in dictating the endothelial cell (EC) response to changes in blood flow, pro-inflammatory response and hence development of atherosclerosis. Previously, our group has identified EC microRNA-155 (miR-155) as one of the key signature dysregulated miRNAs in areas of chronic low magnitude oscillatory shear stress (OSS) in vasculature and OSS models of in-vitro. Hypothesis: we hypothesized that acute induction of OSS mediates EC oxidative stress, inflammation and dysfunction, via dysregulation of EC miR-155. Methods: 12-week old C57B/6J mice were subjected to abdominal aortic coarctation (AAC), a unique model of acute induction of OSS, for 3 days and downstream segments of acute OSS were compared to upstream unidirectional shear stress (USS) segments of the thoracic aorta. Results: Acute OSS resulted in down regulation of EC miR-155 expression and inverse upregulation of EC RhoA and Myosin light chain kinase (MYLK), known targets of miR-155-mediated EC cytoskeleton organization, in OSS segments compared with USS. This was associated with impaired EC dependent relaxation, differential contractile response to phenylephrine, and loss of EC barrier function as evaluated by extravasation of Evans-blue dye assay. In parallel, En-face immunohistochemical staining also showed increased expression of EC nitric oxide synthase (eNOS) along with increased levels of reactive oxygen species (ROS) and nitrotyrosine (NY) formation in OSS segments compared with USS. Conclusions: Together, our studies shed light on the early changes in EC response to acute induction of OSS and resulting down-regulation of EC mir-155, including; oxidative/inflammatory stress, EC dysfunction, loss of barrier function and cytoskeletal changes. Despite the early upregulation of eNOS, it could also potentially synergize with the activation of the RhoA-MYLK pathway in EC oxidative (ROS/NY)/inflammatory stress and associated EC dysfunction. Further studies are in progress to dissect the interplay between these different pathways and their causal relationships as downstream targets of EC miR-155.

scholarly journals MnSOD reduction causes mtDNA damage in HAEC under Oscillatory Shear Stress

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Katherine Quigley ◽  
Karen Fang ◽  
Nelson Jen ◽  
Rongsong Li ◽  
Tzung Hsiai
Keyword(s):  
Shear Stress ◽  
Oscillatory Shear ◽  
Mtdna Damage ◽  
Oscillatory Shear Stress

scholarly journals Quantification of Oscillatory Shear Stress from Reciprocating CSF Motion on 4D Flow Imaging

2021 ◽  
Author(s):  
S. Yamada ◽  
H. Ito ◽  
M. Ishikawa ◽  
K. Yamamoto ◽  
M. Yamaguchi ◽  
...  
Keyword(s):  
Shear Stress ◽  
Oscillatory Shear ◽  
Flow Imaging ◽  
4D Flow ◽  
Oscillatory Shear Stress ◽  
4D Flow Imaging

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

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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