Sustained Increase in Aortic Endothelial Nitric Oxide Synthase Expression In Vivo in a Model of Chronic High Blood Flow

Nadaud, Sophie; Philippe, Monique; Arnal, Jean‐François; Michel, Jean‐Baptiste; Soubrier, Florent

doi:10.1161/01.res.79.4.857

Cited by 204 publications

(153 citation statements)

References 28 publications

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“…The upregulation of eNOS with flow in RAEC-only collagen gels is consistent with the animal studies showing upregulation of eNOS expression by shear stress. 29 No change in thrombomodulin and prostaglandin synthase is at variance with some previous reports, which suggest an upregulation of thromobomodulin 30 and prostacyclin 31,32 by shear stress. However, the magnitude of shear in the gels may not have been sufficient to generate changes in expression of these latter molecules.…”

Section: Protein Analysismentioning

confidence: 58%

A Novel Flow Bioreactor forIn VitroMicrovascularization

Lee

Niklason

2010

Tissue Engineering Part C: Methods

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Although the importance of fluid flow for proper vascular development and function in vivo is well recognized, microvascular formation in response to flow has not been well evaluated in a three-dimensional (3D) environment in vitro. In this study, we developed a novel 3D in vitro perfusion system that allows direct investigation of the effects of shear stress on the development of microvasculature in vitro. This system utilizes a 3D collagen gel for suspension of vascular cells and mesenchymal stem cells, through which flow is directly perfused. We characterized the flow conditions and demonstrate the impact of flow on the development of microvasculature using a coculture of endothelial cells and mesenchymal stem cells. With the unique ability to apply bulk flow through the collagen gels, and to estimate shear stress within the constructs, this perfusion system provides a flexible platform for developing a controllable biomimetic environment that can be adapted for a variety of investigations of microvascularization.

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Section: Protein Analysismentioning

confidence: 58%

A Novel Flow Bioreactor forIn VitroMicrovascularization

Lee

Niklason

2010

Tissue Engineering Part C: Methods

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“…During exercise, blood flow increases to provide muscle with an adequate supply of oxygen and nutrients. It is well documented that flow/shear stress is an important signal regulating eNOS expression in blood vessels (19,27). Consequently, age-associated reductions in physical activity and associated increases in blood flow may remove an important signal for the maintenance of eNOS expression.…”

Section: Discussionmentioning

confidence: 99%

Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries

Woodman

Price

Laughlin

2002

Journal of Applied Physiology

106

123

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. Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries. J Appl Physiol 93: 1685-1690, 2002; 10.1152/ japplphysiol.00461.2002.-We tested the hypothesis that aging decreases endothelium-dependent vasodilation in feed arteries perfusing rat skeletal muscle. In addition, we tested the hypothesis that attenuated vasodilator responses are associated with decreased endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) expression. Soleus feed arteries (SFA) and gastrocnemius feed arteries (GFA) were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats. Feed arteries from the right hindlimb were cannulated with two glass micropipettes for examination of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [adenosine (Ado) or sodium nitroprusside (SNP)] vasodilator function. Feed arteries from the left hindlimb were frozen and used to assess eNOS and SOD-1 protein and mRNA expression. In SFA, endothelium-dependent dilation to ACh was reduced in old rats (0.9 Ϯ 0.04 vs. 0.8 Ϯ 0.03), whereas dilator responses to Ado and SNP were similar in SFA of young and old rats. In GFA, vasodilator responses to ACh, Ado, and SNP were not altered by age. eNOS and SOD-1 protein expression declined with age in SFA (Ϫ71 and Ϫ54%, respectively) but not in GFA. eNOS and SOD-1 mRNA expression were not altered by age in SFA or GFA. Collectively, these data indicate aging induces muscle-specific impairment of endothelium-dependent vascular function in SFA. endothelial nitric oxide synthase; superoxide dismutase; nitric oxide; acetylcholine; sodium nitroprusside RESULTS FROM SEVERAL STUDIES indicate that endothelial function in conduit arteries declines with age in humans and animals (3,4,7,8,10,11,16,23). The endothelial dysfunction induced by aging is characterized by blunted vasodilator responses of conduit arteries to select endothelium-dependent agonists (3,4,7,8,10,11,16,23). The mechanism(s) for the detrimental effects of age on endothelium-dependent dilation is not fully understood; however, age-associated decrements in the ability of endothelial cells to produce and/or release nitric oxide (NO) may contribute to the dysfunction (3,11,16). This speculation is supported by experimental evidence indicating that vasodilation in response to ACh and bradykinin is impaired in aorta from senescent subjects, whereas dilation to sodium nitroprusside (SNP) is not compromised (3,5,16).An age-associated decline in the expression of endothelial NO synthase (eNOS), decreasing local production of NO, is one mechanism that may contribute to impaired endothelium-mediated dilation in conduit arteries of senescent animals. Indeed, age-related reductions eNOS mRNA expression have been reported in aorta of senescent rats (3, 6). Alternatively, decreased expression of Cu/Zn-dependent superoxide dismutase (SOD-1) may contribute to impaired endothelium-mediated dilation by compromising the ability to scavenge superoxide anion (O 2 Ϫ ⅐), decreasing the bio...

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“…In the endothelium, it has been shown that NOS expression is regulated by flowmediated shear stress and is downregulated at sites with low flow. [12][13][14][15] Because AF leads to a loss of organized atrial contraction and to turbulent blood flow in the left atrium, we hypothesized that AF may cause a downregulation of NOS gene expression and function in the left atrial endocardium. The subsequent decrease in NO · concentration may lead to increased expression of PAI-1 and platelet aggregation and ultimately contribute to thrombosis in the left atrium.…”

Section: See P 2764mentioning

confidence: 99%

Downregulation of Endocardial Nitric Oxide Synthase Expression and Nitric Oxide Production in Atrial Fibrillation

et al. 2002

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Background— In the arterial endothelium, laminar flow and cyclical stretch induce expression of NO synthase (NOS). We hypothesized that atrial fibrillation (AF) causes a downregulation of atrial endocardial NOS expression and NO · production. Because NO · has antithrombotic properties, this may contribute to thromboembolism in AF. Methods and Results— In pigs, AF was produced with rapid atrial pacing at 600 bpm for 1 week, whereas controls had atrial pacing at 100 bpm. All animals had catheter ablation of the AV junction and ventricular pacing at 100 bpm. NO · production from freshly isolated tissue was measured by a NO · -specific microelectrode. Left atrial basal and stimulated NO · production was decreased in AF by 73% and 71% ( P <0.01). Endocardial NOS expression, determined by Western analysis, was also significantly decreased by 46%. Expression of the prothombotic protein plasminogen activator inhibitor 1 (PAI-1) is known to be regulated by NO · and was increased in the left atrium by 1.8-fold in AF ( P <0.05). NO · concentration was decreased in the left atrial appendage, although NOS expression was not affected. Neither NOS concentration, NO · levels, nor PAI-1 expression were altered in the aortas or right atria of animals with AF. Conclusions— AF is associated with a marked decrease in endocardial NOS expression and NO · bioavailability and an increase in PAI-1 expression in the left atrium. These data suggest that organized atrial contraction is needed to maintain normal endocardial expression of NOS. It is likely that loss of this antithrombotic enzyme contributes to the thromboembolic phenomena commonly observed in AF.

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Sustained Increase in Aortic Endothelial Nitric Oxide Synthase Expression In Vivo in a Model of Chronic High Blood Flow

Cited by 204 publications

References 28 publications

A Novel Flow Bioreactor forIn VitroMicrovascularization

A Novel Flow Bioreactor forIn VitroMicrovascularization

Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries

Downregulation of Endocardial Nitric Oxide Synthase Expression and Nitric Oxide Production in Atrial Fibrillation

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