Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells.

Nagel, Tobi; Resnick, Nitzan; Atkinson, William J.; Dewey, C. Forbes; Gimbrone, Michael A.

doi:10.1172/jci117410

Cited by 518 publications

(311 citation statements)

References 33 publications

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“…Fourth, anemia may lead to hyperdynamic circulation, which has been shown to modulate the expression of adhesion molecules on vascular endothelial cells by upregulating their production. This may trigger an inflammatory response that leads to thrombus formation in a process similar to atherosclerosis 34, 35. Fifth, anemia may worsen outcomes in stroke because of its relationship with inflammatory mediators; it can upregulate the production of inducible nitric oxide synthase and CXC chemokine receptor 4,36 both of which have been associated with brain damage during ischemia 37, 38…”

Section: Discussionmentioning

confidence: 99%

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke: Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Barlas¹,

Honney

Loke

et al. 2016

JAHA

136

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BackgroundThe impact of hemoglobin levels and anemia on stroke mortality remains controversial. We aimed to systematically assess this association and quantify the evidence.Methods and ResultsWe analyzed data from a cohort of 8013 stroke patients (mean±SD, 77.81±11.83 years) consecutively admitted over 11 years (January 2003 to May 2015) using a UK Regional Stroke Register. The impact of hemoglobin levels and anemia on mortality was assessed by sex‐specific values at different time points (7 and 14 days; 1, 3, and 6 months; 1 year) using multiple regression models controlling for confounders. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to 1 year following stroke. The association was less consistent for men with hemorrhagic stroke. Elevated hemoglobin was also associated with increased mortality, mainly within the first month. We then conducted a systematic review using the Embase and Medline databases. Twenty studies met the inclusion criteria. When combined with the cohort from the current study, the pooled population had 29 943 patients with stroke. The evidence base was quantified in a meta‐analysis. Anemia on admission was found to be associated with an increased risk of mortality in both ischemic stroke (8 studies; odds ratio 1.97 [95% CI 1.57–2.47]) and hemorrhagic stroke (4 studies; odds ratio 1.46 [95% CI 1.23–1.74]).ConclusionsStrong evidence suggests that patients with anemia have increased mortality with stroke. Targeted interventions in this patient population may improve outcomes and require further evaluation.

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Section: Discussionmentioning

confidence: 99%

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke: Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Barlas¹,

Honney

Loke

et al. 2016

JAHA

136

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“…Shear stress and cyclical mechanical strain represent important components of the normal homeostatic mechanisms that regulate gene expression in the endothelium (43)(44)(45)(46)(47), vascular smooth muscle (48), and myocardium (21,22,49). Aberration of this regulatory activity may contribute to the pathological changes that accompany hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Mechanical Strain Increases Expression of the Brain Natriuretic Peptide Gene in Rat Cardiac Myocytes

Liang

Garami³

et al. 1997

Journal of Biological Chemistry

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Using a device that applies cyclical strain (1 Hz) to ventricular cardiocytes cultured on collagen-coated silicone elastomer surfaces, we have demonstrated straindependent increases in brain natriuretic peptide (BNP) secretion, BNP mRNA levels, and expression of a transiently transfected ؊1595 human BNP-luciferase reporter. When actinomycin D (10 M) was introduced concomitantly with the strain stimulus, the strain-induced increase in BNP mRNA was eliminated, and the decay of transcripts was identical in the control and strained cells, indicating the lack of independent effects on transcript stability. Strain-dependent ؊1595 human BNPluciferase activity was completely inhibited by chelerythrine, 2-aminopurine, genistein, and W-7 and only partially or not at all by KN-62, wortmannin, and H-89. The effects of these individual agents paralleled their effects on mitogen-activated protein kinase (MAPK) activity, but not c-Jun N-terminal kinase (JNK) activity, in the cells. Overexpression of wild-type MAPK and, to a lesser extent, JNK increased strain-dependent BNP promoter activity, whereas dominant-negative mutants of MAPK kinase, JNK kinase, or Ras completely blocked strain-dependent reporter activity. These findings provide the first demonstration that mechanical strain can increase myocardial gene expression through a transcriptional mechanism and suggest important roles for MAPK and JNK in mediating this effect.The natriuretic peptides comprise a family of vasoactive hormones that play an important role in the regulation of cardiovascular and renal homeostasis (1). Their natriuretic and vasodepressor properties suggest that they represent endogenous antagonists of the various systems (e.g. renin-angiotensin system and sympathetic nervous system) that support arterial blood pressure under basal conditions and, at times, contribute to the pathophysiology of cardiovascular disease.Atrial natriuretic peptide (ANP), 1 the prototype of the group, is produced primarily in the atria of the heart. ANP is expressed in the cardiac ventricle during development and early neonatal life (2, 3). Expression decays as the animal ages and remains quiescent in the adult unless the ventricle is subjected to hemodynamic overload (i.e. mechanical strain that leads to increased wall stress and subsequently to hypertrophy of the myocardium), as occurs with systemic arterial hypertension or congestive heart failure (4 -7).Brain natriuretic peptide (BNP) is also produced in the heart. Despite the nomenclature, relatively little BNP is expressed in the mammalian brain (the exception being the porcine brain, where the peptide was identified originally). Expression of BNP in the heart is lower than that of ANP under basal conditions, and the atrial/ventricular ratio of expression is considerably less than that seen with ANP (8). Ventricular expression of BNP is activated in a fashion similar to ANP in pathophysiological states associated with hemodynamic overload (9, 10). At some stages of advanced congestive heart failure, circulating BNP le...

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“…Examination of candidate genes has revealed that many potentially atherosclerosis-related gene products display shear-sensitive expression by endothelium, including VCAM-1, MCP-1, ICAM-1, eNOS, platelet-derived growth factors, transforming growth factor-␤1, and endothelin. [7][8][9][10][11] More recently, microarray-based studies have demonstrated that expression of hundreds of genes display sensitivity to both the duration and nature (eg, laminar versus turbulent) of shear imposed on endothelial cells. 12 The sensitivity of endothelium to shear forces is most obviously manifest through changes in cell morphology: the cells elongate, the cell outline and its cytoskeleton becomes highly oriented in the direction of shear stress, and the profile of the cells becomes substantially more flattened when they are exposed to shear stress.…”

mentioning

confidence: 99%

Assembly and Reorientation of Stress Fibers Drives Morphological Changes to Endothelial Cells Exposed to Shear Stress

Noria

McCue

et al. 2004

The American Journal of Pathology

152

122

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Fluid shear stress greatly influences the biology of vascular endothelial cells and the pathogenesis of atherosclerosis. Endothelial cells undergo profound shape change and reorientation in response to physiological levels of fluid shear stress. These morphological changes influence cell function; however, the processes that produce them are poorly understood. We have examined how actin assembly is related to shear-induced endothelial cell shape change. To do so, we imposed physiological levels of shear stress on cultured endothelium for up to 96 hours and then permeabilized the cells and exposed them briefly to fluorescently labeled monomeric actin at various time points to assess actin assembly. Alternatively, monomeric actin was microinjected into cells to allow continuous monitoring of actin distribution. Actin assembly occurred primarily at the ends of stress fibers, which simultaneously reoriented to the shear axis, frequently fused with neighboring stress fibers, and ultimately drove the poles of the cells in the upstream and/or downstream directions. Actin polymerization occurred where stress fibers inserted into focal adhesion complexes, but usually only at one end of the stress fiber. Neither the upstream nor downstream focal adhesion complex was preferred. Changes in actin organization were accompanied by translocation and remodeling of cell-substrate adhesion complexes and transient formation of punctate cell-cell adherens junctions. These findings indicate that stress fiber assembly and realignment provide a novel mode by which cell morphology is altered by mechanical signals.

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Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells.

Cited by 518 publications

References 33 publications

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke: Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke: Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Mechanical Strain Increases Expression of the Brain Natriuretic Peptide Gene in Rat Cardiac Myocytes

Assembly and Reorientation of Stress Fibers Drives Morphological Changes to Endothelial Cells Exposed to Shear Stress

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