Bi-phasic activation of eNOS in response to uni-axial cyclic stretch is mediated by differential mechanisms in BAECs

Takeda, H.; Komori, Kimihiro; Nishikimi, Naomichi; Nimura, Yuji; Sokabe, Masahiro; Naruse, Keiji

doi:10.1016/j.lfs.2005.12.051

Cited by 47 publications

(38 citation statements)

References 41 publications

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“…These results suggested that MEK1 mediates stretchinduced SGK-1 expression. Because mechanical stretch also stimulates signals such as PI3K 24 and Egr-1, 11 we determined their roles in mechanical stretch-regulated expression of SGK-1. PI3K inhibitor (Ly294002) did not inhibit stretchinduced increases in both SGK-1 mRNA as shown in Figure 2E.…”

Section: Mek1 Signaling Pathway Mediates Mechanical Stretch-induced Smentioning

confidence: 99%

The Mechanical Stress–Activated Serum-, Glucocorticoid-Regulated Kinase 1 Contributes to Neointima Formation in Vein Grafts

Cheng

Wang

et al. 2010

Circulation Research

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Objective: The objective of this study is to identify mechanisms of mechanical stretch on neointima formation. Methods and Results: By a microarray analysis, we found that mechanical cyclic stretch (15% elongation) stimulated the transcription of SGK-1 (serum-, glucocorticoid-regulated kinase-1). Mechanical stretch-induced SGK-1 mRNA expression was blocked by actinomycin D. The mechanism for the SGK-1 expression involved MEK1 but not p38 or JNK signaling pathway. SGK-1 activation in response to stretch is blocked by insulin-like growth factor (IGF)-1 receptor inhibitor and mammalian target of rapamycin complex (mTORC)2 inhibitor (Ku-0063794) but not mTORC1 inhibitor (rapamycin). Mechanical stretch-induced bromodeoxyuridine incorporation was reduced by 83.5% in venous SMCs isolated from SGK-1 knockout mice. In contrast, inhibition of Akt, another downstream signal of PI3K resulted in only partial inhibition of mechanical stretch-induced proliferation of venous SMCs. Mechanical stretch also induced phosphorylation and nuclear exportation of p27 kip1 , whereas knockout of SGK-1 attenuated this effect of mechanical stretch on p27 kip1. In vivo, we found that placement of a vein graft into artery increased SGK-1 expression. Knockout of SGK-1 effectively prevented neointima formation in vein graft. There is significant lower level of p27 kip1 located in the nucleus of neointima cells in SGK-1 knockout mice compared with that of wild-type vein graft. In addition, we also found that wire injury of artery or growth factors in vitro increased expression of SGK-1. Key Words: mechanical stretch Ⅲ serum-, glucocorticoid-regulated kinase-1 Ⅲ neointima formation Ⅲ mTORC Ⅲ mammalian target of rapamycin complex I ncreased growth of venous smooth muscle cells (SMCs) is a hallmark of vein graft failure. [1][2][3][4] After implantation of a vein graft into the arterial circulation, the venous wall is immediately exposed to mechanical stimuli. Those include arterial pressure, wall tension, shear stress, and pulsatile flow, all of which modulate graft physiology. [5][6][7] Such alteration could lead to the activation of many intracellular signaling pathways. Mechanical stress could also stimulate the synthesis and/or secretion of various bioactive molecules including platelet-derived growth factor (PDGF), basic fibroblast growth factor, and the transcriptional factors. 8 -10 Recently, we have shown that mechanical stretch stimulates expression and activation of insulin-like growth factor (IGF)-1 and its receptor in venous SMCs, and we found that activated IGF-1R/phosphatidylinositol 3-kinase (PI3K) is essential for mechanical stretch-induced proliferation of venous SMCs. 11 However, the downstream targets of IGF-1/ PI3K signaling that mediate mechanical stretch-induced proliferation of venous SMCs are still unknown. Conclusions:Belonging to the AGC subfamily, the catalytic domain of SGK-1 (serum-, glucocorticoid-regulated kinase-1) is 54% identical to that of AKT, and it shares common downstream substrates with AKT. 12,13 Activation...

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Section: Mek1 Signaling Pathway Mediates Mechanical Stretch-induced Smentioning

confidence: 99%

The Mechanical Stress–Activated Serum-, Glucocorticoid-Regulated Kinase 1 Contributes to Neointima Formation in Vein Grafts

Cheng

Wang

et al. 2010

Circulation Research

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“…[47][48][49] NO formation was also increased by cyclic stretch, as detected by increased endothelial cyclic GMP levels. 50 The effect of NOS inhibition on cyclic stretchinduced ET-1 release has not been investigated (to our knowledge).…”

Section: Endothelium: Stress: Pressure/cyclic Stretchmentioning

confidence: 98%

Nitric Oxide Inhibition of Endothelin-1 Release in the Vasculature

Rapoport

2014

Hypertension

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A key function of endothelial derived nitric oxide (NO) is to limit the constrictor capacity of endothelin (ET)-1.1,2 Thus, an imbalance between NO and ET-1 can result in ET-1-dependent increased vascular tone.1 Indeed, the importance of sustained, NO inhibition of the ET-1 drive to increase tone is exemplified in vivo by the rapid, ET-1-mediated arterial pressure elevation after acute NO synthase (NOS) inhibition. Moreover, the ET-1 pressor effect after NOS inhibition is independent of other pressor systems and, thus, reflects the relative importance of NO suppression of this ET-1 drive.2 Two, nonmutually exclusive mechanisms thought to underlie the ET-1 dependency of the increased vascular tone responsible for the NOS inhibitor-induced pressure elevation are (1) NO inhibition of constriction to endogenously released ET-1.1,2 This mechanism is essentially supported by demonstrations that NOS inhibitor enhanced the constrictor effects of exogenous ET-1 in several in vivo and ex vivo preparations. 3-14Thus, an assumption underlying these observations is that the constrictor actions of exogenous and endogenous ET-1 are similarly affected by NO; (2) NO inhibition of ET-1 release. 1,2Although the detailed mechanism underlying the NO inhibition of acute ET-1 release has not been clearly established, possibilities include decreased conversion of the immediate precursor to ET-1, big ET-1, to ET-1 15 and inhibition of pathways involved in the exocytosis of Weibel-Palade bodies, 16 endothelial granules that store ET-1. 17 However, it should be noted that in vivo findings that actually demonstrate the fundamental phenomenon of NO inhibition of ET-1 release are generally lacking.2 Thus, studies purported to demonstrate NO inhibition of ET-1 release have relied largely on isolated vessels and cultured endothelium, as described herein.This review assessed these in vitro findings, with a specific focus toward elucidating the mechanism underlying the NO-mediated negative regulation of ET-1-dependent increased arterial pressure, as demonstrated after acute NOS inhibitor in vivo.2 Findings referred to are mainly those of ET-1 release rather than contractility (eg, those in which ET receptor antagonist prevented the NOS inhibitor-induced decreased flow/increased pressure/tension). 12,18-25 The rationale for this emphasis is that findings based on contractility could reflect NOS inhibitor enhancement of ET-1 constriction rather than increased ET-1 release. Furthermore, we also focus on whether laminar shear stress influences the manifestation of NO inhibition of ET-1 release. That is, the endothelium of arteries that are anatomically linear is subjected to high levels of shear stress while, for example, at bifurcated arterial locations is subjected to low levels of shear stress, regions associated with atherosclerosis. 26 Acute NOS Inhibition/No Donors and ET-1 Release ArteriesIn rat heart perfused at constant flow, increased amounts of ET-1 were detected in the coronary effluent of samples collected for the final 5 to 15 minutes ...

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“…As early as the 1990s, several in vitro studies provided evidence that physiological levels of cyclic strain are able to increase eNOS gene expression and protein (18) and eNOS activity (19) in cultured endothelial cells. The upregulation of eNOS in response to cyclic stretch is mediated via [Ca 2ϩ ] i increase through stretch-activated channels in an early phase, followed by activation of the PI3K/Akt pathway in a later phase (398). In BAECs cultured within distensible tubes, reduced wall distensibility altered pulse pressure-induced eNOS/Akt mechanosignaling and subsequent cytoprotection against oxidant stress (326).…”

Section: Stretch Versus Shear: Differential Impact On Enos Activationmentioning

confidence: 99%

eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues

Balligand¹,

Feron²,

Dessy³

2009

Physiological Reviews

391

328

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Nitric oxide production in response to flow-dependent shear forces applied on the surface of endothelial cells is a fundamental mechanism of regulation of vascular tone, peripheral resistance, and tissue perfusion. This implicates the concerted action of multiple upstream "mechanosensing" molecules reversibly assembled in signalosomes recruiting endothelial nitric oxide synthase (eNOS) in specific subcellular locales, e.g., plasmalemmal caveolae. Subsequent short- and long-term increases in activity and expression of eNOS translate this mechanical stimulus into enhanced NO production and bioactivity through a complex transcriptional and posttranslational regulation of the enzyme, including by shear-stress responsive transcription factors, oxidant stress-dependent regulation of transcript stability, eNOS regulatory phosphorylations, and protein-protein interactions. Notably, eNOS expressed in cardiac myocytes is amenable to a similar regulation in response to stretching of cardiac muscle cells and in part mediates the length-dependent increase in cardiac contraction force. In addition to short-term regulation of contractile tone, eNOS mediates key aspects of cardiac and vascular remodeling, e.g., by orchestrating the mobilization, recruitment, migration, and differentiation of cardiac and vascular progenitor cells, in part by regulating the stabilization and transcriptional activity of hypoxia inducible factor in normoxia and hypoxia. The continuum of the influence of eNOS in cardiovascular biology explains its growing implication in mechanosensitive aspects of integrated physiology, such as the control of blood pressure variability or the modulation of cardiac remodeling in situations of hemodynamic overload.

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Bi-phasic activation of eNOS in response to uni-axial cyclic stretch is mediated by differential mechanisms in BAECs

Cited by 47 publications

References 41 publications

The Mechanical Stress–Activated Serum-, Glucocorticoid-Regulated Kinase 1 Contributes to Neointima Formation in Vein Grafts

The Mechanical Stress–Activated Serum-, Glucocorticoid-Regulated Kinase 1 Contributes to Neointima Formation in Vein Grafts

Nitric Oxide Inhibition of Endothelin-1 Release in the Vasculature

eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues

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