Phenotypic changes in rat and guinea pig coronary microvascular endothelium after culture: loss of nitric oxide synthase activity

Lang, Derek; Bell, John P.; Bayraktutan, Ulvi; Small, Gary; Shah, Ajay M.; Lewis, Malcolm J.

doi:10.1016/s0008-6363(98)00336-8

Cited by 18 publications

(16 citation statements)

References 38 publications

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“…On the other hand, it is well known that working with endothelial cells at higher passages may be artifact-prone because they hardly produce any NO. 50 In addition, it is important to distinguish between shear stress and (cyclic) stretch which per se are very different biomechanical forces both in terms of direction (unidirectional versus bidirectional deformation) and relative strength (typically stretch is 3 to 4 orders of magnitude greater than shear stress).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Glutathione Peroxidase Offsets Stretch-Induced Proatherogenic Gene Expression in Human Endothelial Cells

Wagner

Kautz

Fricke

et al. 2009

ATVB

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Objective-Localization of atherosclerotic plaques typically correlates with areas of biomechanical strain where shear stress is decreased while stretch, thought to promote atherogenesis through enhanced oxidative stress, is increased. Methods and Results-In human cultured endothelial cells, nitric oxide synthase expression was exclusively shear stress-dependent whereas expression of glutathione peroxidase-1 (GPx-1), but not that of Cu 2ϩ /Zn 2ϩ -superoxide dismutase or Mn 2ϩ -superoxide dismutase, was upregulated solely in response to cyclic stretch. GPx-1 expression was also enhanced in isolated mouse arteries perfused at high pressure. Combined pharmacological and decoy oligodeoxynucleotide blockade revealed that activation of p38 MAP kinase followed by nuclear translocation of CCAAT/enhancer binding protein plays a pivotal role in stretch-induced GPx-1 expression in human endothelial cells. Antisense oligodeoxynucleotide knockdown of GPx-1 reinforced both their capacity to generate hydrogen peroxide and the transient stretch-induced expression of CD40, monocyte chemoatractant protein-1, and vascular cell adhesion molecule-1. Consequently, THP-1 monocyte adhesion to the GPx-1-depleted cells was augmented. Conclusions-Stretch-induced proatherosclerotic gene expression in human endothelial cells seems to be hydrogen peroxide-mediated. The concomitant rise in GPx-1 expression, but not that of other antioxidant enzymes, may comprise an adaptive mechanism through which the cells maintain their antiatherosclerotic properties in spite of a decreased bioavailability of nitric oxide. Key Words: glutathione peroxidase Ⅲ oxidative stress Ⅲ cyclic stretch Ⅲ endothelial cells Ⅲ atherosclerosis A therosclerotic plaques are often located at arterial bifurcations and curvatures. 1,2 Although the primary risk factors for atherosclerosis (ie, diabetes, dyslipidemia, hypertension, and cigarette smoking) contribute to pathophysiological mechanisms which affect the endothelium in general, they do not explain the focal nature of the disease. Otherwise, it is well known that biomechanical forces exerted on the vessel wall by the flowing blood tend to vary at these predilection sites due to oscillations in blood flow. 3 As a result, laminar shear stress is reduced, whereas volume (pressure)-dependent deformation of the vessel wall is enhanced. 3 Whereas laminar shear stress protects arteries from developing atherosclerosis by maintaining endothelial cell nitric oxide (NO) synthesis, cyclic deformation promotes atherosclerosis through an increased formation of reactive oxygen species (ROS), namely superoxide anions (O 2 Ϫ ). Both radicals rapidly neutralize each other, hence reducing the level of biologically active NO even further. 4 Whereas cyclic stretch in endothelial cells, presumably through activation of protein kinase C and subsequent assembly of NOX-2, 5,6 initially triggers the formation of O 2 Ϫ , this is rapidly converted to hydrogen peroxide (H 2 O 2 ) by the various superoxide dismutases (SOD) present in these cells....

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Section: Discussionmentioning

confidence: 99%

Upregulation of Glutathione Peroxidase Offsets Stretch-Induced Proatherogenic Gene Expression in Human Endothelial Cells

Wagner

Kautz

Fricke

et al. 2009

ATVB

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“…Because our analysis of cAMP dynamics after combined selective inhibition of PDE3 and PDE4 activities in HUVECs and HMVECs had shown that these treatments resulted in an approximately additive effect on cAMP levels, we had initially predicted that dual PDE3 and PDE4 inhibition would have similarly affected migration in an additive manner. Although a possible explanation for the apparent antagonistic effect of combined PDE3 and PDE4 inhibition on migration of these cells may stem from the impact of VEGF-induced increases in cGMP (Ferrara, 1999;Lang et al, 1999;Wohlfart et al, 1999; Rivero- Fig. 4.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Cell Cyclic Nucleotide Phosphodiesterases and Regulated Cell Migration: Implications in Angiogenesis

Netherton

Maurice²

2004

Mol Pharmacol

114

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Angiogenesis is necessary during embryonic development and wound healing but can be detrimental in pathologies, including cancer. Because initiation of angiogenesis involves migration and proliferation of vascular endothelial cells (VECs) and cAMPelevating agents inhibit these events, such agents may represent a novel therapeutic avenue to controlling angiogenesis. Intracellular cAMP levels are regulated by their synthesis by adenylyl cyclases and hydrolysis by cyclic nucleotide phosphodiesterases (PDEs). In this report, we show that human VECs express variants of PDE2, PDE3, PDE4, and PDE5 families and demonstrate that the levels of these enzymes differ in VECs derived from aorta, umbilical vein, and microvascular structures. Selective inhibition of PDE2 did not increase cAMP in any VECs, whether in the absence or presence of forskolin, but it did inhibit migration of all VECs studied. Inhibition of PDE4 activity decreased migration, and in conjunction with forskolin, increased cAMP in all VECs studied. PDE3 inhibition potentiated forskolin-induced increases in cAMP and inhibited migration in VECs derived from aorta and umbilical vein but not in microvascular VECs. In experiments with combinations of PDE2, PDE3, and PDE4 inhibitors, a complex interaction between the abilities of these agents to limit human VEC migration was observed. Overall, our data are consistent with the hypothesis that PDE subtype inhibition allows different effects in distinct VEC populations and indicate that these agents may represent novel therapeutic agents to limit angiogenesis in complex human diseases.

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“…The present study was therefore designed to investigate the reciprocal relationship between coronary endothelial cell growth and the concurrent expression and activity of the enzymes, namely, eNOS and NAD(P)H oxidase that are associated with the regulation of endothelial cell redox state. All the experiments outlined in the current study were carried out using early-passage cultured rat CMEC in order to avoid the effects of changes in coronary endothelial cell phenotype on enzyme expression and activity [30]. Significant increases in eNOS mRNA and protein expressions, eNOS activity and consequently in nitrite generation, the ultimate breakdown product of NO, were observed in proliferating versus confluent CMEC.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide synthase and NAD(P)H oxidase modulate coronary endothelial cell growth

Bayraktutan

2004

Journal of Molecular and Cellular Cardiology

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Reactive oxygen species (ROS) including nitric oxide (NO) and superoxide anion (O 2 -) are associated with cell migration, proliferation and many growth-related diseases. The objective of this study was to determine whether there was a reciprocal relationship between rat coronary microvascular endothelial cell (CMEC) growth and activity/expressions (mRNA and protein) of endothelial NO synthase (eNOS) and

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Phenotypic changes in rat and guinea pig coronary microvascular endothelium after culture: loss of nitric oxide synthase activity

Cited by 18 publications

References 38 publications

Upregulation of Glutathione Peroxidase Offsets Stretch-Induced Proatherogenic Gene Expression in Human Endothelial Cells

Upregulation of Glutathione Peroxidase Offsets Stretch-Induced Proatherogenic Gene Expression in Human Endothelial Cells

Vascular Endothelial Cell Cyclic Nucleotide Phosphodiesterases and Regulated Cell Migration: Implications in Angiogenesis

Nitric oxide synthase and NAD(P)H oxidase modulate coronary endothelial cell growth

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