Disruption of cytoskeletal structures mediates shear stress-induced endothelin-1 gene expression in cultured porcine aortic endothelial cells.

Morita, Toshisuke; Kurihara, Hiroki; Maemura, Koji; Yoshizumi, Masao; Yazaki, Yoshio

doi:10.1172/jci116757

Cited by 113 publications

(56 citation statements)

References 37 publications

(35 reference statements)

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“…Various conditions contribute to the increased vascular wall shear forces observed in sickle cell disease, including the higher viscosity of blood from subjects with sickle cell disease (39) and the increased blood flow rates secondary to the severe anemia and low systemic vascular resistance. Discrepant, tissuespecific vasomotor effects may be mediated by changes in the balance of shear-induced endothelial cell production of vasoconstrictor peptides, like ET-1 and PDGF-BB (40)(41)(42)(43)(44)(45), and shear-induced production of vasodilators like nitric oxide (46)(47)(48)(49)(50), and prostacyclins (51 ). Tissue hypoxia is common in subjects with sickle cell disease and may also contribute to local vasoconstriction.…”

Section: Resultsmentioning

confidence: 99%

Sickle erythrocytes, after sickling, regulate the expression of the endothelin-1 gene and protein in human endothelial cells in culture.

Phelan¹,

Perrine²,

Brauer³

et al. 1995

J. Clin. Invest.

103

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The molecular defect in sickle cell disease resides in the 11 globin gene, with consequent defects in erythrocytes only, suggesting that the vascular occlusion and vasomotor instability which characterize this disease are the result of interactions between abnormal sickle erythrocytes and cells of the blood vessel wall. We explored whether sickle erythrocytes may have effects on vascular tone, exclusive of adhesion events. Exposure of human endothelial cells in culture to previously sickled sickle erythrocytes resulted in a four to eight-fold transcriptional induction of the gene encoding the potent vasoconstrictor endothelin-1 (ET-1). Unsickled sickle erythrocytes or normal erythrocytes exposed to "sickling" conditions had no effect on ET-1 gene induction. Contact of the sickled erythrocytes with the endothelium was not required. Elevations in the ET-1 transcript peaked at 3 h after exposure and persisted for up to 24 h. Four to sixfold increases in the amount of ET-1 peptide was released into the medium surrounding the endothelial cells after exposure to sickled sickle erythrocytes. This is the first demonstration of the regulation of gene expression in endothelial cells as a result of interaction with sickle cells, with induction of genes encoding vasoconstrictors. Furthermore, these findings suggest that sickle erythrocytes may have the capacity to affect local vasomotor tone directly. (J. Clin. Invest. 1995. 96: 1145-1151

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Section: Resultsmentioning

confidence: 99%

Sickle erythrocytes, after sickling, regulate the expression of the endothelin-1 gene and protein in human endothelial cells in culture.

Phelan¹,

Perrine²,

Brauer³

et al. 1995

J. Clin. Invest.

103

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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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“…Since PTx and CTx had no significant effect on shear-dependent activation of JNK (Fig. 5), ␣ 12 /␣ 13 . Cell lysates were immunoprecipitated with an anti-HA antibody followed by MBP phosphorylation, SDS-PAGE, and autoradiography.…”

Section: Shear Stress Stimulates Jnk1 In a Time-and Thresholdmentioning

confidence: 96%

Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells

Sipos

et al. 1997

Journal of Biological Chemistry

251

261

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Shear stress differentially regulates production of many vasoactive factors at the level of gene expression in endothelial cells that may be mediated by mitogenactivated protein kinases, including extracellular signal-regulated kinase (ERK) and N-terminal Jun kinase (JNK). Here we show, using bovine aortic endothelial cells (BAEC), that shear stress differentially regulates ERK and JNK by mechanisms involving G i2 and pertussis toxin (PTx)-insensitive G-protein-dependent pathways, respectively. Shear activated ERK with a rapid, biphasic time course (maximum by 5 min and basal by 30-min shear exposure) and force dependence (minimum and maximum at 1 and 10 dyn/cm 2 shear stress, respectively). PTx treatment prevented shear-dependent activation of ERK1/2, consistent with a G i -dependent mechanism. In contrast, JNK activity was maximally turned on by a threshold level of shear force (0.5 dyn/ cm 2 or higher) with a much slower and prolonged time course (requiring at least 30 min to 4 h) than that of ERK. Also, PTx had no effect on shear-dependent activation of JNK. To further define the shear-sensitive ERK and JNK pathways, vectors expressing hemagglutinin epitope-tagged ERK (HA-ERK) or HA-JNK were cotransfected with other vectors by using adenoviruspolylysine in BAEC. Expression of the mutant ␣ i2 (G203), antisense G␣ i2 and a dominant negative Ras (N17Ras) prevented shear-dependent activation of HA-ERK, while that of ␣ i2 (G204) and antisense ␣ i3 did not. Expression of a G␤/␥ scavenger, the carboxyl terminus of ␤-adrenergic receptor kinase (␤ARK-ct), and N17Ras inhibited sheardependent activation of HA-JNK. Treatment of BAEC with genistein prevented shear-dependent activation of ERK and JNK, indicating the essential role of tyrosine kinase(s) in both ERK and JNK pathways. These results provide evidence that 1) G i2 -protein, Ras, and tyrosine kinase(s) are upstream regulators of shear-dependent activation of ERK and 2) that shear-dependent activation of JNK is regulated by mechanisms involving G␤/␥, Ras, and tyrosine kinase(s).Endothelial cells lining the inner vessel wall are in direct contact with flowing blood, which generates a frictional force, hemodynamic shear stress, acting on the surface of the endothelium. Hemodynamic shear stress controls vascular tone, vessel wall remodeling, interaction of blood cells with endothelium, coagulation, and fibrinolysis (1). The focal pattern of atherosclerotic lesions in areas of low and/or unstable shear stress further highlights the importance of shear stress in the atherogenic process (2, 3). Endothelial cells play a key role in shear-dependent vascular changes, sensing shear stress by an unidentified mechanoreceptor(s) followed by production of autocrine and paracrine factors (1). For example, hemodynamic shear stress selectively and differentially regulates production of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, platelet-derived growth factor-B, basic fibroblast growth factor, transforming growth factor ␤-1, tissue plasminogen activator,...

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Disruption of cytoskeletal structures mediates shear stress-induced endothelin-1 gene expression in cultured porcine aortic endothelial cells.

Cited by 113 publications

References 37 publications

Sickle erythrocytes, after sickling, regulate the expression of the endothelin-1 gene and protein in human endothelial cells in culture.

Sickle erythrocytes, after sickling, regulate the expression of the endothelin-1 gene and protein in human endothelial cells in culture.

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

Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells

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