© 2000 American Heart Association, Inc.
Vascular Biology |
Angiotensin II Stimulates Endothelial Vascular Cell Adhesion Molecule-1 via Nuclear Factor-
B Activation Induced by Intracellular Oxidative Stress
From INSERM U460 (M.E.P., W.G., F.S., J.-B.M.) and INSERM U430 (A.N.), Paris, and INSERM U397 (J.-F.A.), Toulouse, France.
Correspondence to Dr Maria E. Pueyo, INSERM U460, Faculté de Médecine Xavier Bichat, 16, rue Henri Huchard, 75018 Paris, France. E-mail pueyo{at}infobiogen.fr
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract—The recruitment of monocytes via the endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) is a key step in the formation of the initial lesion in atherosclerosis. Because angiotensin (Ang) II may be involved in this process, we investigated its role on the signaling cascade leading to VCAM-1 expression in endothelial cells. Ang II stimulates mRNA and protein expression of VCAM-1 in these cells via the AT1 receptor. This effect was enhanced by NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, and blocked by pyrrolidinedithiocarbamate, an antioxidant molecule. Ang II activated the redox-sensitive transcription factor nuclear factor-
B and stimulated the degradation of both inhibitor of B
(IB)
and IBß with different kinetics. The degradation of
IBs induced by Ang II was not modified by incubation with exogenous
superoxide dismutase and catalase, suggesting that this effect was not
mediated by the extracellular production of
O2-. In contrast, rotenone and antimycin, 2
inhibitors of the mitochondrial respiratory chain,
inhibited the Ang II–induced IB degradation, showing that
generation of reactive oxygen species in the mitochondria is involved
on Ang II action. BXT-51702, a glutathione peroxidase mimic, inhibited
the effect of Ang II, and aminotriazole, an inhibitor of
catalase, enhanced it, suggesting a role for
H2O2 in IB degradation. This is confirmed by
experiments showing that Ang II stimulates the intracellular
production of H2O2 in
endothelial cells. These results demonstrate that Ang
II induced an intracellular oxidative stress in
endothelial cells, which stimulates IB degradation
and nuclear factor-B activation. This activation enhances the
expression of VCAM-1 and probably other genes involved in the
early stages of atherosclerosis.
Key Words: endothelium • nuclear factor-B • IB • superoxide anions • hydrogen peroxide
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
One of the earliest detectable cellular responses in the formation of atherosclerotic lesions is the focal recruitment of leukocytes by intact endothelium.1 2 This localized accumulation of leukocytes is mediated by the endothelial expression of specific adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, or platelet–endothelial cell adhesion molecule-1.3 VCAM-1, which is focally expressed by endothelial cells in atherosclerotic lesions,2 4 appears to be correlated with increased accumulation of mononuclear cells.5 The expression of VCAM-1 in endothelial cells is enhanced by inflammatory mediators or cytokines. This regulation of VCAM-1 expression occurs at the transcriptional level and is mediated, at least in part, via the redox-sensitive transcription factor nuclear factor-
B
(NF-B).6 Activated NF-B is involved in the
expression of several proinflammatory genes and is present in
endothelial cells in the early lesions of
atherosclerosis.7 In unstimulated
endothelial cells, the predominant form of NF-B is
present in the cytoplasm as a heterodimer of p50 and p65 subunits
complexed with inhibitor of B (IB) proteins. After cell
stimulation, IB is degraded, releasing NF-B and thus allowing its
translocation to the nucleus.8 Among IBs, IB and
IBß play a major role in the regulation of NF-B. These 2
molecules are structurally similar, but their degradation and their
patterns of expression differ.9 Inducers of NF-B
activation, such as tumor necrosis factor- (TNF-), phorbol
12-myristate 13-acetate, or UV radiation cause oxidative
stress, suggesting that the induction of radical oxygen species (ROS)
is a common signal to a wide variety of NF-B–inducing
conditions.10 Angiotensin (Ang) II, the main effector of the renin-angiotensin system, plays an essential role in the regulation of blood pressure but is also involved in remodeling of the arterial wall.11 It has recently been shown that antagonists of AT1 Ang II receptors decrease the formation of the atheromatous plaque in several animal models of atherosclerosis12 13 and that Ang II increases leukocyte adhesion to the endothelium in vitro.14 Given that VCAM-1 expression in endothelial cells is inhibited by AT1 receptor antagonists in vivo,15 we hypothesized that Ang II could directly modulate VCAM-1 expression in these cells. Indeed, endothelial cells express AT1 receptors, which activate different intracellular pathways16 and modulate several cell functions.17 Moreover, Ang II stimulates the generation of ROS in smooth muscle cells via the activation of NADH/NADPH oxidases18 19 and could be also implicated in ROS production in endothelial cells.
The aim of the present study was to evaluate whether Ang II
regulates the expression of VCAM-1 in endothelial cells
and whether the transcription factor NF-B was involved in this
regulation. We also investigated the effect of Ang II on the
degradation of IB proteins in endothelial cells and
attempted to identify the ROS implicated in this degradation and the
site of their production.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Materials
DMEM, HEPES, horse serum, and trypsin/EDTA were obtained from Life Technologies Inc. Ang II, penicillin, streptomycin, superoxide dismutase (SOD), catalase, NG-nitro-L-arginine methyl ester (L-NAME), pyrrolidinedithiocarbamate (PDTC), and aminotriazole were from Sigma Chemical Co. Antibodies against VCAM-1, NF-
B p65, NF-B p50, IB, and IBß were purchased from
Santa Cruz Biotechnologies. Irbesartan was kindly provided by Sanofi
Recherche (Montpellier, France), and PD123177 was provided by Dr P.
Janiack (Synthelabo, Paris, France). The glutathione peroxidase mimic,
BXT-51702, was a gift from OXIS International (Bonneuil sur Marne,
France).
Cell Culture
Rat aortic endothelial cells were isolated as
previously described.20 This method provides pure cell
preparations (>95% of endothelial cells), as shown by
immunostaining with a specific antibody against rat
endothelial cells.21 Cells from passages 1
to 3 were used in these studies.
Semiquantitative Analysis of VCAM-1 mRNA Expression by
RT-PCR
Extraction of total RNA and reverse transcriptase
(RT)—polymerase chain reaction (PCR) are described in detail
elsewhere.15 Oligo primers for VCAM-1 included 5'-CAC CTC
CCC CAA GAA TAC AGA-3' (sense) and 5'-GCT CAT CCT CAA CAC CCA CAG-3'
(antisense), which amplify a 476-bp fragment. The primers for the rat
ß-actin were 5'-TGG AAT CCT GTG GCA TCC ATG AAA C-3' (antisense) and
5'-TAA AAC GCA GCT CAG TAA CAG TCC G-3' (sense). VCAM-1 mRNA expression
was normalized to the housekeeping gene ß-actin mRNA expression.
Western Blot Analysis
Cells were serum-deprived for 24 hours and incubated with
10-7 Ang II during times indicated in Results.
When used, antagonists were preincubated for 30 minutes
before the addition of Ang II. After incubation, cells were lysed by
use of 10 mmol/L Tris-HCl, pH 7.4, 1% Triton, 0.5% Nonidet P-40,
0.5 mmol/L sodium orthovanadate, 150 mmol/L NaCl, 1
mmol/L EGTA, 1 mmol/L EDTA, 1 mmol/L NaF, 30 mmol/L
pyrophosphate sodium, 1 µg/mL aprotinin, and 1 mmol/L serine
protease inhibitor (Interchim). The cell lysates were
centrifuged for 20 minutes at 14 000g.
Protein concentrations were determined by the Bradford assay.
Whole-cell lysates (25 µg) were separated by SDS-PAGE and transferred
to a nitrocellulose membrane (Hybond, Amersham). Immunodetection was
performed by using Renaissance reagents (Amersham).
Preparation of Nuclear Extracts and Electrophoretic Mobility
Shift Assay
After treatment of endothelial cells for 1 hour
with 10-7 Ang II, nuclear proteins were prepared
as previously described.22
Gel-shift assays were performed with a commercial kit according to the
instructions of the manufacturer (Promega). The NF-B
oligonucleotide probe used (5'-AGT TGA GGG GAC TTT CCC
AGG C-3') was labeled with [
-32P]ATP by use
of T4 polynucleotide kinase. Nuclear
proteins were incubated for 20 minutes with the labeled probe and
migrated in a 4% polyacrylamide gel.
The specificity of the binding reaction was determined by coincubating
duplicate samples with either 100-fold molar excess of unlabeled
oligonucleotide probe or anti–NF-B antibodies
(anti-p65 and anti-p50).
Determination of H2O2 Production
The generation of intracellular peroxides in rat aortic
endothelial cells was monitored with a
fluorescent dye, 2',7'-dichlorofluorescein
diacetate (DCFH-DA, Molecular Probes).23 Serum-deprived
cells were stimulated with 10-7 Ang II for 1
hour. Forty-five minutes before the end of the incubation, DCFH-DA was
added at a final concentration of 10-5 mol/L.
Cells were then scraped off into 1 mL of distilled water, sonicated,
and centrifuged. The fluorescence of supernatants was
measured with a spectrofluorometer (HITACHI F-2000) at 485-nm
excitation and 525-nm emission. Data were expressed in arbitrary
fluorescence units and normalized with respect to the protein
content in each culture dish.
Statistical Analysis
Data are expressed as mean±SEM. Groups were compared by ANOVA.
Differences were considered significant at P<0.05.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Ang II Stimulates Expression of VCAM-1 via AT1 Receptor and NF-
B PathwayVCAM-1 mRNA expression, evaluated by RT-PCR, was stimulated by Ang II in a dose-dependent manner (Figure 1A
). Ang II also enhanced VCAM-1 protein
expression, as evaluated by Western blot (Figure 1B). These
effects were inhibited by the AT1-specific
antagonist irbesartan but not by the
AT2 receptor antagonist PD123177
(Figure 2), indicating that Ang II action
was mediated by the AT1 receptor.
|
|
Because nitric oxide (NO) and ROS are implicated in the regulation of
VCAM-1 expression through the redox-sensitive transcription factor
NF-B, we evaluated the effect of the NO synthase
inhibitor L-NAME and of the antioxidant PDTC on Ang
II–induced VCAM-1 expression. Figure 3
shows that L-NAME enhanced basal and, to a lesser extent, Ang
II–induced VCAM-1 expression. Conversely, PDTC significantly decreased
both basal and Ang II–induced VCAM-1 expression. Because PDTC is an
antioxidant and a metal chelator known to inhibit the transcription
factor NF-B24 and the VCAM-1 promoter possesses
specific DNA binding motifs for NF-B,6 we hypothesized
that the Ang II–induced VCAM-1 expression was mediated via this
transcription factor. To confirm this, we tested whether Ang II was
activating the transcription factor NF-B by use of an
electrophoretic mobility shift assay. Figure 4 shows that Ang II increased
the nuclear translocation of NF-B. This effect was abolished by an
excess of cold probe, and preincubation with anti-p65 and anti-p50
antibodies induced a supershift.
|
|
Ang II Activates NF-B by Inducing Differential
Degradation of IB and IBß
The translocation of NF-B to the nucleus requires the release
of NF-B from its cytoplasmic inhibitors, the IB
proteins. These proteins are degraded after stimulation of
NF-B–activating factors. We investigated the effect of Ang II on
IB and IBß degradation on endothelial cells.
Ang II treatment resulted in a rapid degradation of IB (within 15
minutes), with a maximal effect after 30 minutes of stimulation (Figure 5). IB was synthesized de novo
after 1 hour. Ang II also induced the degradation of IBß, but this
degradation was observed after only 30 minutes, and IBß was not
synthesized de novo after a 2-hour treatment with Ang II (Figure 5) and remained at low levels for 24 hours (data not shown).
|
Degradation of IBs Is Dependent on Mitochondrial ROS
Release
Having demonstrated that Ang II stimulates the disappearance of
immunoreactive IBs and given that the induction of ROS is a common
signal to a wide variety of NF-B–inducing conditions, we next
determined whether the degradation of IB was dependent on the
production of ROS. For this purpose, we used PDTC, a
nonspecific antioxidant. Our results show that PDTC inhibits the Ang
II–induced IB degradation (Figure 6A). To better understand this
phenomenon, we used SOD, an enzyme that dismutates
O2- into
H2O2, and catalase, which
degrades H2O2. SOD does not
modify the Ang II–induced IB degradation, and no effect was
observed when cells were incubated with SOD plus catalase (Figure 6B). During the short time of incubation (1 hour),
both enzymes may remain in the extracellular compartment, and they do
not affect intracellular ROS,25 so that our results
suggest that Ang II–induced IB degradation was not dependent on
oxidant stress occurring on the cell surface.
|
Thus, we next studied the involvement of intracellular ROS.
Mitochondrial respiration constitutes one of the most important sources
of ROS in the cell. Figure 6C
shows that 2
inhibitors of the mitochondrial respiratory chain, rotenone
and antimycin, inhibit Ang II–induced IB degradation. This suggests
that Ang II–induced degradation of IBs was provoked by ROS, which
were most likely formed within the mitochondria. As a consequence of
the abundance of manganese SOD in the mitochondria,26 most
of the O2- generated in this
organelle is converted into
H2O2. Thus, we investigated
the role of intracellular
H2O2 by interfering with
its intracellular degradation, a role devoted to glutathione peroxidase
and catalase. BXT-51702, a potent glutathione peroxidase mimic, which
catalyzes the degradation of
H2O2 by
glutathione,27 inhibited the effect of Ang II on the
degradation of IB and IBß. In contrast, aminotriazole, an
inhibitor of catalase but also of glutathione peroxidase,
which increases intracellular levels of
H2O2, enhanced the IB
degradation induced by Ang II (Figure 6D).
Detection of Generation of ROS by Ang II
To further evaluate the Ang II–induced oxidative stress, we
assessed the production of
O2- after Ang II stimulation of
endothelial cells with 2 different methods,
lucigenin-enhanced chemiluminescence and electron spin resonance by
using 5,5'-dimethyl-1-pyrroline N-oxide as a spin
trap.28 We failed to detect any
O2- production in
response to Ang II in endothelial cells. In contrast,
we have previously reported the production of
O2- by bradykinin with the use
of these 2 methods.28 Because these techniques mainly
measured extracellular production of
O2-, we conclude that Ang II
does not enhance extracellular
O2- production. Next,
we evaluate the intracellular production of
H2O2 with DCFH-DA, a probe
used to detect intracellular
H2O2 in a variety of cells,
including endothelial cells. Figure 7 shows that endothelial
cells incubated with 10-7 mol/L Ang II exhibited
an increase in intracellular DCFH-DA fluorescence, indicating
the production of intracellular
H2O2 in response to Ang II.
This production may be implicated in the Ang II–induced IB
degradation.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Upregulation of adhesion molecules, such as VCAM-1, occurs at sites of lesion formation in early atherosclerosis.4 Hypertension, one of the known clinical risk factors for atherosclerosis, increases endothelial VCAM-1 expression.15 29 In the present study, we demonstrated that Ang II directly stimulates VCAM-1 expression in endothelial cells, suggesting that the Ang II effect on VCAM-1 expression observed in vivo is not merely an indirect effect via its hypertensive action.
The Ang II action on VCAM-1 expression in endothelial cells was inhibited by irbesartan, an AT1 antagonist, in agreement with studies showing that the AT1 receptor–mediated signal is predominant in this cell type.16 These in vitro data are in accord with in vivo studies showing that AT1 receptor antagonists decrease VCAM-1 expression in endothelial cells.15
Because NO decreases the expression of VCAM-1,30 31 we evaluated the effect of L-NAME, a NO synthase inhibitor, on Ang II–induced VCAM-1 expression. NO blockade inhibited the basal expression of VCAM-1 in endothelial cells but produced only a discrete increase in this expression in Ang II–stimulated cells, suggesting that endogenous levels of NO in endothelial cells, at least in vitro, are not sufficient to limit Ang II–induced VCAM-1 expression, despite the simultaneous stimulation of NO production by Ang II.32
A key component of the cytokine-inducible VCAM-1 expression is
the redox-sensitive transcription factor NF-B.6 In the
present study, we demonstrate that Ang II activates NF-B
in endothelial cells, suggesting that the upregulation
of VCAM-1 expression in response to Ang II is mediated by this
transcription factor. However, the regulatory regions of the VCAM-1
gene are composed of multiple binding elements, which are recognized by
a large number of transcription factors. The
cytokine-induced transcriptional enhancer in the VCAM-1
promoter requires combinatorial interactions of NF-B with other
nuclear activators, such as stimulatory protein-1,
interferon regulatory factor-1, and activator
protein-1.33 34 35 Ang II activates the
transcription factor, AP-1, but there are no data available about the
effect of Ang II on Sp-1 or IRF-1. Further studies will be necessary to
evaluate the role of these transcription activators in the
modulation of Ang II–induced NF-B transactivation of the VCAM-1
promoter.
Translocation of NF-B to the nucleus requires the degradation of the
cytoplasmic inhibitory proteins IB and IBß.
Recent studies concluded that some NF-B activators
induce degradation of IB but not IBß, suggesting that these
2 proteins are regulated differentially. We demonstrated that Ang II
stimulates the degradation of IB and IBß, but the kinetics
of degradation were different: whereas IB degradation was rapid
and transient, IBß degradation was slower and persisted for at
least 24 hours. This differential regulation of the pools of IB
and IBß may allow fine tuning of the activation/repression of
NF-B by Ang II. Indeed, some NF-B inducers would cause a rapid
but transient activation of NF-B by primarily affecting IB
complexes, whereas the others would cause persistent activation of
NF-B by affecting both IB and IBß
complexes.36 In endothelial cells, TNF-
has been shown to activate NF-B rapidly and persistently, in
contrast to other agents, such as phorbol 12-myristate
13-acetate, which causes a slow and transient
activation.37 In view of our results, it appears that the
overall activation of NF-B by Ang II consists of 2 overlapping
phases, a rapid transient phase mediated through IB and a
persistent phase mediated through IBß.
The behavior of agonists that activate NF-B greatly depends
on the cell type involved.37 It is of interest to point
out that Ang II does not modify IBß levels in rat aortic smooth
muscle cells, whereas it stimulates the degradation of IB in this
cell type (data not shown). Moreover, others have demonstrated that
TNF- fails to modulate IBß but decreases IB levels in
smooth muscle cells,38 and we have observed that TNF-
increases the degradation of IB and IBß in
endothelial cells (M.E.P. et al, unpublished data,
1998). These data suggest that the regulation of IBß and possibly
the nature of the NF-B response (transient versus sustained) differ
between smooth muscle and endothelial cells. The
divergent NF-B regulation in smooth muscle cells and
endothelial cells may have potential functional
consequences that are of particular interest in view of the proximity
of these 2 cell types within the vessel wall.
Several lines of evidence indicate that ROS are implicated in the
activation of NF-B and the degradation of IBs.10
Because it is known that Ang II stimulates oxidative stress in various
cell types,18 including endothelial
cells,32 we investigated whether the ROS generated in
response to Ang II were implicated in the degradation of IBs. This
is shown by the inhibitory effect of PDTC on the Ang
II–induced IB degradation. Pharmacological studies that used
aminotriazole or BXT-51702 suggest that
H2O2 and/or derivatives
mediate Ang II–induced IB degradation and agree with data showing
that ROS, in particular,
H2O2, act as second
messengers in the activation of NF-B.39 This hypothesis
is further supported by our results showing that Ang II enhanced
H2O2 production in
endothelial cells. One can suppose that Ang II shares
some of these ROS-dependent pathways leading to NF-B activation with
other activators, such as TNF-. For example, BXT-51702,
a potent glutathione peroxidase mimic that inhibits the Ang II–induced
IB degradation, also decreases the VCAM-1 expression induced by
TNF-40 as well as other adhesion molecules
activated by NF-B.41 However, the critical
steps in the signal transduction cascade of IB degradation by ROS
remain to be determined.
Recently, the understanding of the downstream pathways implicated in
the regulation of IB degradation has advanced to a great extent.
Phosphorylation seems to be necessary for the
degradation of IB, but not of IBß.9 Two IB
kinases, IKK-1 and IKK-2, have been identified as responsible for the
phosphorylation of IB.42 43 These
IKKs are activated by a NF-B–inducing kinase, NIK, a member
of the mitogen-activated protein kinase-3
family,44 which, in turn, is activated by
TGFß-activated kinase-1.45 Antioxidants specifically
inhibit the IKK activity stimulated by TNF-.46 However,
their effect on NIK activation is unknown at present. Further
studies will be necessary to determine the link between ROS and these
signaling pathways and the role of Ang II in their modulation.
In conclusion, proinflammatory cytokines, via the induction of
VCAM-1 expression, are thought to participate in monocyte accumulation
in the vessel wall and contribute to atherosclerotic lesions. The
present study demonstrates that Ang II, like cytokines,
could participate in inducing these events via
endothelial cells. The activation of the transcription
factor NF-B by Ang II, leading to the upregulation of
proinflammatory genes, may explain, at least in part, the diminution of
monocytes adhesion induced by Ang II receptor
antagonists.13 Endothelial
cells are the principal target of plasma Ang II, because little of the
Ang II generated in the plasma passes to the media and vice
versa.47 This chronic phenotypic modulation of
endothelial cells by plasma Ang II could be involved in
the development of atherosclerotic lesions and participate in the
relation between the activation of the renin-angiotensin
system and the risk of
atherosclerosis.48 49
|
Acknowledgments |
|---|
This work was supported by INSERM and by a grant from SANOFI Recherche (Montpellier, France). M.E.P. was supported by a grant from SANOFI Recherche, and W.G. was supported by a grant from the Société de Secours des Amis des Sciences. We are indebted to Dr J. Chaudière for providing the BXT-51702 and for helpful discussions.
Received March 31, 1999; accepted September 17, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Davies MJ, Woolf N, Rowles PM, Pepper J. Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br Heart J. 1988;60:459–464.
2.
Hongmei L, Cybulsky MI, Gimbrone MA, Libby P. An
atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable
mononuclear leukocyte adhesion molecule, in rabbit aortic
endothelium. Arterioscler Thromb. 1993;13:197–204.
3. Chia MC. The role of adhesion molecules in atherosclerosis. Crit Rev Clin Lab Sci. 1998;35:573–602.[Medline] [Order article via Infotrieve]
4.
Nakashima Y, Raines EW, Plum AS, Breslow JL, Ross R.
Upregulation of VCAM-1 and ICAM-1 at
atherosclerosis-prone site on the
endothelium in the ApoE-deficient mouse.
Arterioscler Thromb Vasc Biol. 1998;18:842–851.
5.
O’Brien KD, McDonald TO, Chati A, Allen MD, Alpers
CE. Neovascular expression of E-selectin, ICAM-1 and VCAM-1 in human
atherosclerosis and their relation to intimal leukocyte
content. Circulation. 1996;93:672–682.
6. Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 1995;9:899–909.[Abstract]
7. Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, Page M, Kaltschmidt C, Bauerle P, Neumeier D. Activated transcription factor nuclear factor-kappa B is presented in the atherosclerotic lesion. J Clin Invest. 1996;97:1715–1722.[Medline] [Order article via Infotrieve]
8.
Henkel T, Machleidt T, Alkalay I, Kronke M, Benneriah
Y, Bauerle PA. Rapid proteolysis of IB- is necessary for
activation of transcription factor NF-B. Nature. 1993;365:182–185.[Medline]
[Order article via Infotrieve]
9.
Weil R, Laurent-Winter C, Israël A. Regulation
of IBß degradation. J Biol Chem. 1997;272:9942–9949.
10.
Muller JM, Rupec RA, Baeuerle PA. Study of gene
regulation by NFB and AP-1 in response to reactive oxygen
intermediates. Methods. 1997;11:301–312.[Medline]
[Order article via Infotrieve]
11. Matsusaka T, Ichikawa I. Biological functions of angiotensin and its receptors. Annu Rev Physiol. 1997;59:395–412.[Medline] [Order article via Infotrieve]
12. Schuch JR, Blahn DJ, Frierdich GE, McMahon EG, Blaine EH. Differential effects of renin-angiotensin system blockade in atherogenesis in cholesterol fed-rabbits. J Clin Invest. 1993;91:1453–1458.
13. Keidar S, Attias J, Smith J, Breslow JL, Hayek T. The angiotensin-II receptor antagonist, losartan, inhibits LDL lipid peroxidation and atherosclerosis in apolipoprotein E-deficient mice. Biochem Biophys Res Commun. 1997;236:622–625.[Medline] [Order article via Infotrieve]
14. Kim JA, Berliner JA, Nadler JL. Angiotensin II increases monocyte binding to endothelial cells. Biochem Biophys Res Commun. 1996;226:862–868.[Medline] [Order article via Infotrieve]
15.
Luvara G, Pueyo ME, Philippe M, Mandet C, Savoie F,
Henrion D, Michel JB. Chronic blockade of NO synthase activity induces
a proinflammatory phenotype in the arterial wall.
Arterioscler Thromb Vasc Biol. 1998;18:1408–1416.
16. Pueyo ME, N'Diaye N, Michel JB. Angiotensin II-elicited signal transduction via AT1 receptors in endothelial cells. Br J Pharmacol. 1996;118:79–84.[Medline] [Order article via Infotrieve]
17. Pueyo ME, Michel JB. Angiotensin II receptors in endothelial cells. Gen Pharmacol. 1997;29:691–696.[Medline] [Order article via Infotrieve]
18.
Griendling KK, Minieri CA, Ollerenshaw JD, Alexander
RW. Angiotensin II stimulates NADH and NADPH oxidase
activity in cultured vascular smooth muscle cells. Circ Res. 1994;74:1141–1148.
19. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. J Clin Invest. 1996;97:1916–1923.[Medline] [Order article via Infotrieve]
20. Battle T, Arnal JF, Challah M, Michel JB. Selective isolation of rat aortic wall layers and their cell types in culture application to converting enzyme activity measurement. Tissue Cell. 1994;26:943–955.[Medline] [Order article via Infotrieve]
21. Duijvestijn AM, van Goor H, Klatter F, Majoor GD, van Bussel E, Breda V, Vriesman JC. Antibodies defining rat endothelial cells: RECA-1, a pan-endothelial cell-specific monoclonal antibody. Lab Invest. 1992;66:459–466.[Medline] [Order article via Infotrieve]
22.
Ollivier V, Parry GCN, Cobb RR, Deprost D, Mackman N.
Elevated cyclic AMP inhibits NF-kappa B-mediated transcription in human
monocytic cells and endothelial cells. J
Biol Chem. 1996;271:20828–20835.
23. Carter WO, Narayanan PK, Robinson JP. Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells. J Leukoc Biol. 1994;55:253–258.[Abstract]
24.
Schreck R, Meier B, Mannel DN, Dröge W, Baeuerle
PA. Dithiocarbamates as potent inhibitors of nuclear
factor B activation in intact cells. J Exp Med. 1992;175:1181–1194.
25.
Freeman BA, Young SL, Crapo JD. Liposome-mediated
augmentation of superoxide dismutase in endothelial
cells prevents oxygen injury. J Biol Chem. 1983;258:12534–12542.
26. Harris E. Regulation of antioxidant enzymes. FASEB J. 1992;6:2675–2683.[Abstract]
27. Chaudière J, Yadan JC, Erdelmeier I, Tailhan-Lomont C, Moutet M. Design of new selenium-containing mimics of glutathione peroxidase. In: Paolett R, ed. Oxidative Processes and Antioxidants. New York, NY: Raven Press Ltd; 1994:165–184.
28.
Barbacanne MA, Rami J, Michel JB, Souchard JP, Philippe
M, Besombes JP, Bayard F, Arnal JF. Estradiol increases rat aorta
endothelium-derived relaxing factor (EDRF) activity
without changes in endothelial NO synthase gene
expression: possible role of decreased
endothelium-derived superoxide anion
production. Cardiovasc Res. 1999;41:672–681.
29.
Mervaala EM, Muller DN, Park JK, Schmidt F, Lohn M,
Breu V, Dragun D. Monocyte infiltration and adhesion molecules in a rat
model of high human renin hypertension. Hypertension. 1999;33:389–395.
30.
Spiecker M, Peng HB, Liao JK. Inhibition of
endothelial vascular cell adhesion molecule-1
expression by nitric oxide involves the induction and nuclear
translocation of I kappa B alpha. J Biol Chem. 1997;272:30969–30974.
31.
Kahn BV, Harrison DG, Olbrych MT, Alexander RW, Medford
RM. Nitric oxide regulates VCAM-1 expression and redox-sensitive
transcriptional events in human vascular endothelial
cells. Proc Natl Acad Sci U S A. 1996;93:9114–9119.
32. Pueyo ME, Arnal JF, Rami J, Michel JB. Angiotensin II stimulates the production of NO and peroxynitrite in endothelial cells. Am J Physiol. 1998;43:C214–C220.
33.
Neish AS, Khachigian LM, Park A, Baichwal VR, Collins
T. Sp1 is a component of the cytokine-inducible enhancer in the
promoter of vascular cell adhesion molecule-1. J Biol
Chem. 1995;270:28903–28909.
34. Neish AS, Read MA, Thanos D, Pine R, Maniatis T, Collins T. Endothelial interferon regulatory factor 1 cooperates with NF-kappa B as a transcriptional activator of vascular cell adhesion molecule-1. Mol Cell Biol. 1995;15:2558–2569.[Abstract]
35.
Ahmad M, Theofanidis P, Medford RM. Role of activating
protien-1 in the regulation of the vascular cell adhesion molecule-1
expression by tumor necrosis factor-. J Biol
Cell. 1998;273:4616–4621.
36. Thompson JE, Phillips RJ, Erdjument-Bromage H, Tempst P, Ghosh S. I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B. Cell. 1995;80:573–582.[Medline] [Order article via Infotrieve]
37.
Johnson DR, Douglas I, Jahnke A, Ghosh S, Pober JS. A
sustained reduction in IkB-ß may contribute to persistent NFB
activation in human endothelial cells. J
Biol Chem. 1996;271:16317–16322.
38.
Bourcier T, Sukhova G, Libby P. The nuclear factor
kappa-B signaling pathway participates in dysregulation of vascular
smooth muscle cells in vitro and in human
atherosclerosis. J Biol Chem. 1997;272:15817–15824.
39. Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J. 1996;10:709–720.[Abstract]
40.
D’Alessio P, Moutet M, Coudrier E, Darquenne S,
Chaudière J. ICAM-1 and VCAM-1 expressions induced by
TNF- are inhibited by a glutathione peroxidase mimic.
Free Radic Biol Med. 1998;24:979–987.[Medline]
[Order article via Infotrieve]
41.
Moutet M, D’Alessio P, Malette P, Devaux V,
Chaudière J. Glutathione peroxidase mimics prevent TNF-
and neutrophil-induced endothelial alterations.
Free Radic Biol Med. 1998;25:270–281.[Medline]
[Order article via Infotrieve]
42.
Mercurio F, Zhu HY, Murray BW, Shevchenko A, Bennett
BL, Li JW, Young DB, Barbosa M, Mann M. IKK-1 and IKK-2:
cytokine-activated I kappa B kinases essential for
NF-kappa B activation. Science. 1997;278:860–866.
43. DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M. A cytokine-responsive I kappa B kinase that activates the transcription factor NF-kappa B. Nature. 1997;388:548–554.[Medline] [Order article via Infotrieve]
44.
Malinin NL, Boldin MP, Kovalendo AV, Wallach D.
MAP3K-related kinase involved in NF-B induction by TNF, CD95
and IL-1. Nature. 1997;385:540–544.[Medline]
[Order article via Infotrieve]
45. Ninomiya-Tsuiji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K. The kinase TAK1 can activated the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 1999;398:252–256.[Medline] [Order article via Infotrieve]
46. Spiecker M, Darius H, Kaboth K, Hübner F, Liao JK. Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants. J Leukoc Biol. 1999;63:732–739.[Abstract]
47. Danser AHJ, Chowdury S, de Lannoy LM, Van Der Giessen WJ, Saxena PR, Schalekamp MADH. Conversion and degradation of (125I) labelled angiotensin I in isolated perfused porcine coronary and carotid arteries. Cardiovasc Res. 1995;29:798–795.
48. Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Laragh JH. Association of renin-sodium profile with the risk of myocardial infarction in patients with hypertension. N Engl J Med. 1991;324:1098–1104.[Abstract]
49. Alderman MH, Ooi WL, Cohen H, Madhavan S, Sealey JE, Laragh JM. Plasma renin activity: a risk factor for myocardial infarction in hypertensive patients. Am J Hypertens. 1997;10:1–8.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  E. M. de Cavanagh, M. Ferder, F. Inserra, and L. Ferder Angiotensin II, mitochondria, cytoskeletal, and extracellular matrix connections: an integrating viewpoint Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H550 - H558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Koh, P. C. Oh, and M. J. Quon Does reversal of oxidative stress and inflammation provide vascular protection? Cardiovasc Res, March 1, 2009; 81(4): 649 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, S. Yang, S. Hu, M. A. Choudhry, K. I. Bland, and I. H. Chaudry Estrogen prevents intestinal inflammation after trauma-hemorrhage via downregulation of angiotensin II and angiotensin II subtype I receptor Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G1131 - G1137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhang, S.-h. Zhou, S.-P. Zhao, Q.-m. Liu, X.-p. Li, and X.-Q. Shen Irbesartan attenuates Ang II-induced BMP-2 expression in human umbilical vein endothelial cells Vascular Medicine, August 1, 2008; 13(3): 239 - 245. [Abstract] [PDF]
|
|
|
|
|
|
M. Takahashi, E. Suzuki, R. Takeda, S. Oba, H. Nishimatsu, K. Kimura, T. Nagano, R. Nagai, and Y. Hirata Angiotensin II and tumor necrosis factor-{alpha} synergistically promote monocyte chemoattractant protein-1 expression: roles of NF-{kappa}B, p38, and reactive oxygen species Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2879 - H2888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bledsoe, B. Shen, Y.-Y. Yao, M. Hagiwara, B. Mizell, M. Teuton, D. Grass, L. Chao, and J. Chao Role of Tissue Kallikrein in Prevention and Recovery of Gentamicin-Induced Renal Injury Toxicol. Sci., April 1, 2008; 102(2): 433 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Wosten-van Asperen, R. Lutter, J. J. Haitsma, M. P. Merkus, J. B. van Woensel, C. M. van der Loos, S. Florquin, B. Lachmann, and A. P. Bos ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin Eur. Respir. J., February 1, 2008; 31(2): 363 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Barthel, M. W. Johansson, D. M. McNamee, and D. F. Mosher Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma J. Leukoc. Biol., January 1, 2008; 83(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Carluccio, M. A. Ancora, M. Massaro, M. Carluccio, E. Scoditti, A. Distante, C. Storelli, and R. De Caterina Homocysteine induces VCAM-1 gene expression through NF-{kappa}B and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2344 - H2354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Henke, R. Schmidt-Ullrich, R. Dechend, J.-K. Park, F. Qadri, M. Wellner, M. Obst, V. Gross, R. Dietz, F. C. Luft, et al. Vascular Endothelial Cell Specific NF-{kappa}B Suppression Attenuates Hypertension-Induced Renal Damage Circ. Res., August 3, 2007; 101(3): 268 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lewis, N. Stefanovic, J. Pete, A. C. Calkin, S. Giunti, V. Thallas-Bonke, K. A. Jandeleit-Dahm, T. J. Allen, I. Kola, M. E. Cooper, et al. Lack of the Antioxidant Enzyme Glutathione Peroxidase-1 Accelerates Atherosclerosis in Diabetic Apolipoprotein E-Deficient Mice Circulation, April 24, 2007; 115(16): 2178 - 2187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Cassis, D. L. Rateri, H. Lu, and A. Daugherty Bone Marrow Transplantation Reveals That Recipient AT1a Receptors Are Required to Initiate Angiotensin II-Induced Atherosclerosis and Aneurysms Arterioscler. Thromb. Vasc. Biol., February 1, 2007; 27(2): 380 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Mehta and K. K. Griendling Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system Am J Physiol Cell Physiol, January 1, 2007; 292(1): C82 - C97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Camello-Almaraz, P. J. Gomez-Pinilla, M. J. Pozo, and P. J. Camello Mitochondrial reactive oxygen species and Ca2+ signaling Am J Physiol Cell Physiol, November 1, 2006; 291(5): C1082 - C1088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Jie, M. C. Verhaar, M.-J. M. Cramer, K. van der Putten, C. A. J. M. Gaillard, P. A. Doevendans, H. A. Koomans, J. A. Joles, and B. Braam Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors Am J Physiol Renal Physiol, November 1, 2006; 291(5): F932 - F944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Paravicini and R. M. Touyz Redox signaling in hypertension Cardiovasc Res, July 15, 2006; 71(2): 247 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M Ridker, E. Danielson, N. Rifai, R. J. Glynn, and for the Val-MARC Investigators Valsartan, Blood Pressure Reduction, and C-Reactive Protein: Primary Report of the Val-MARC Trial Hypertension, July 1, 2006; 48(1): 73 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V Teplitsky, Y Shoenfeld, and A Tanay The renin-angiotensin system in lupus: physiology, genes and practice, in animals and humans Lupus, June 1, 2006; 15(6): 319 - 325. [Abstract] [PDF]
|
|
|
|
|
|
A. E. Vendrov, N. R. Madamanchi, Z. S. Hakim, M. Rojas, and M. S. Runge Thrombin and NAD(P)H Oxidase-Mediated Regulation of CD44 and BMP4-Id Pathway in VSMC, Restenosis, and Atherosclerosis Circ. Res., May 26, 2006; 98(10): 1254 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Douillette, A. Bibeau-Poirier, S.-P. Gravel, J.-F. Clement, V. Chenard, P. Moreau, and M. J. Servant The Proinflammatory Actions of Angiotensin II Are Dependent on p65 Phosphorylation by the I{kappa}B Kinase Complex J. Biol. Chem., May 12, 2006; 281(19): 13275 - 13284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, Y. Liu, H. Liu, P. L. Hermonat, and J. L. Mehta Molecular Dissection of Angiotensin II-Activated Human LOX-1 Promoter Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1163 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Petnehazy, K. Y. Stokes, K. C. Wood, J. Russell, and D. N. Granger Role of Blood Cell-Associated AT1 Receptors in the Microvascular Responses to Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 313 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cai Hydrogen peroxide regulation of endothelial function: Origins, mechanisms, and consequences Cardiovasc Res, October 1, 2005; 68(1): 26 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. De Ciuceis, F. Amiri, P. Brassard, D. H. Endemann, R. M. Touyz, and E. L. Schiffrin Reduced Vascular Remodeling, Endothelial Dysfunction, and Oxidative Stress in Resistance Arteries of Angiotensin II-Infused Macrophage Colony-Stimulating Factor-Deficient Mice: Evidence for a Role in Inflammation in Angiotensin-Induced Vascular Injury Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2106 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Basta, G. Lazzerini, S. Del Turco, G. M. Ratto, A. M. Schmidt, and R. De Caterina At Least 2 Distinct Pathways Generating Reactive Oxygen Species Mediate Vascular Cell Adhesion Molecule-1 Induction by Advanced Glycation End Products Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1401 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M Touyz Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension: role of angiotensin II Exp Physiol, July 1, 2005; 90(4): 449 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chalupsky and H. Cai Endothelial dihydrofolate reductase: Critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase PNAS, June 21, 2005; 102(25): 9056 - 9061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, Y. Ma, J. Zhang, J. Cheng, and J. Du A New Cellular Signaling Mechanism for Angiotensin II Activation of NF-{kappa}B: An I{kappa}B-Independent, RSK-Mediated Phosphorylation of p65 Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1148 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Shah Role of the renin-angiotensin system in the pathogenesis of preeclampsia Am J Physiol Renal Physiol, April 1, 2005; 288(4): F614 - F625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Petnehazy, K. Y. Stokes, J. M. Russell, and D. N. Granger Angiotensin II Type-1 Receptor Antagonism Attenuates the Inflammatory and Thrombogenic Responses to Hypercholesterolemia in Venules Hypertension, February 1, 2005; 45(2): 209 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Bongartz, M. J. Cramer, P. A. Doevendans, J. A. Joles, and B. Braam The severe cardiorenal syndrome: 'Guyton revisited' Eur. Heart J., January 1, 2005; 26(1): 11 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Li and A. M Shah Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1014 - R1030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Bowler, M. Nicks, K. Tran, G. Tanner, L.-Y. Chang, S. K. Young, and G. S. Worthen Extracellular Superoxide Dismutase Attenuates Lipopolysaccharide-Induced Neutrophilic Inflammation Am. J. Respir. Cell Mol. Biol., October 1, 2004; 31(4): 432 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin and R. M. Touyz From bedside to bench to bedside: role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H435 - H446. [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh, J. W. Son, J. Y. Ahn, D. S. Kim, D. K. Jin, H. S. Kim, S. H. Han, Y.-H. Seo, W.-J. Chung, W. C. Kang, et al. Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients Hypertension, August 1, 2004; 44(2): 180 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Mamputu and G. Renier Advanced glycation end-products increase monocyte adhesion to retinal endothelial cells through vascular endothelial growth factor-induced ICAM-1 expression: inhibitory effect of antioxidants J. Leukoc. Biol., June 1, 2004; 75(6): 1062 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Paul, K. W.S. Ko, L. Li, V. Yechoor, M. A. McCrory, A. J. Szalai, and L. Chan C-Reactive Protein Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice Circulation, February 10, 2004; 109(5): 647 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Koh, J. Y. Ahn, S. H. Han, D. S. Kim, D. K. Jin, H. S. Kim, M.-S. Shin, T. H. Ahn, I. S. Choi, and E. K. Shin Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients J. Am. Coll. Cardiol., September 3, 2003; 42(5): 905 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dandona, V. Kumar, A. Aljada, H. Ghanim, T. Syed, D. Hofmayer, P. Mohanty, D. Tripathy, and R. Garg Angiotensin II Receptor Blocker Valsartan Suppresses Reactive Oxygen Species Generation in Leukocytes, Nuclear Factor-{kappa}B, in Mononuclear Cells of Normal Subjects: Evidence of an Antiinflammatory Action J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4496 - 4501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Scortegagna, M. A. Morris, Y. Oktay, M. Bennett, and J. A. Garcia The HIF family member EPAS1/HIF-2{alpha} is required for normal hematopoiesis in mice Blood, September 1, 2003; 102(5): 1634 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Desideri, M. C. Bravi, M. Tucci, G. Croce, M. C. Marinucci, A. Santucci, E. Alesse, and C. Ferri Angiotensin II Inhibits Endothelial Cell Motility Through an AT1-Dependent Oxidant-Sensitive Decrement of Nitric Oxide Availability Arterioscler. Thromb. Vasc. Biol., July 1, 2003; 23(7): 1218 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Mazza, A. Goodman, G. Lombardo, A. Vanella, and N. G. Abraham Heme Oxygenase-1 Gene Expression Attenuates Angiotensin II-Mediated DNA Damage in Endothelial Cells Experimental Biology and Medicine, May 1, 2003; 228(5): 576 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Li and A. M. Shah Mechanism of Endothelial Cell NADPH Oxidase Activation by Angiotensin II. ROLE OF THE p47phox SUBUNIT J. Biol. Chem., March 28, 2003; 278(14): 12094 - 12100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Sohn, F. Krotz, S. Zahler, T. Gloe, M. Keller, K. Theisen, T. M Schiele, V. Klauss, and U. Pohl Crucial role of local peroxynitrite formation in neutrophil-induced endothelial cell activation Cardiovasc Res, March 1, 2003; 57(3): 804 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tepel, M. van der Giet, M. Statz, J. Jankowski, and W. Zidek The Antioxidant Acetylcysteine Reduces Cardiovascular Events in Patients With End-Stage Renal Failure: A Randomized, Controlled Trial Circulation, February 25, 2003; 107(7): 992 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Iwagaki, N. Choe, Y. Li, D. R. Hemenway, and E. Kagan Asbestos Inhalation Induces Tyrosine Nitration Associated with Extracellular Signal-Regulated Kinase 1/2 Activation in the Rat Lung Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 51 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Yan, D. Kim, T. Aizawa, and B. C. Berk Functional Interplay Between Angiotensin II and Nitric Oxide: Cyclic GMP as a Key Mediator Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 26 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Landmesser and H. Drexler Oxidative stress, the renin-angiotensin system, and atherosclerosis Eur. Heart J. Suppl., January 1, 2003; 5(suppl_A): A3 - A7. [Abstract] [PDF]
|
|
|
|
|
|
N. Werner and G. Nickenig AT1 receptors in atherosclerosis: biological effects including growth, angiogenesis, and apoptosis Eur. Heart J. Suppl., January 1, 2003; 5(suppl_A): A9 - A13. [Abstract] [PDF]
|
|
|
|
|
|
R. De Caterina and C. Manes Inflammation in early atherogenesis: impact of ACE inhibition Eur. Heart J. Suppl., January 1, 2003; 5(suppl_A): A15 - A24. [Abstract] [PDF]
|
|
|
|
|
|
Q. N. Diep, F. Amiri, R. M. Touyz, J. S. Cohn, D. Endemann, M. F. Neves, and E. L. Schiffrin PPAR{alpha} Activator Effects on Ang II-Induced Vascular Oxidative Stress and Inflammation Hypertension, December 1, 2002; 40(6): 866 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Brasier, A. Recinos III, and M. S. Eledrisi Vascular Inflammation and the Renin-Angiotensin System Arterioscler. Thromb. Vasc. Biol., August 1, 2002; 22(8): 1257 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Lorenzo, M. Ruiz-Ortega, Y. Suzuki, M. Ruperez, V. Esteban, T. Sugaya, and J. Egido Angiotensin III Activates Nuclear Transcription Factor-{kappa}B in Cultured Mesangial Cells Mainly via AT2 Receptors: Studies with AT1 Receptor-Knockout Mice J. Am. Soc. Nephrol., May 1, 2002; 13(5): 1162 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Morigi, D. Macconi, C. Zoja, R. Donadelli, S. Buelli, C. Zanchi, M. Ghilardi, and G. Remuzzi Protein Overload-Induced NF-{kappa}B Activation in Proximal Tubular Cells Requires H2O2 through a PKC-Dependent Pathway J. Am. Soc. Nephrol., May 1, 2002; 13(5): 1179 - 1189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, E. Crockett, D. H. Wang, J. J. Galligan, G. D. Fink, and A. F. Chen Gene Transfer of Endothelial NO Synthase and Manganese Superoxide Dismutase on Arterial Vascular Cell Adhesion Molecule-1 Expression and Superoxide Production in Deoxycorticosterone Acetate-Salt Hypertension Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 249 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Nickenig and D. G. Harrison The AT1-Type Angiotensin Receptor in Oxidative Stress and Atherogenesis: Part I: Oxidative Stress and Atherogenesis Circulation, January 22, 2002; 105(3): 393 - 396. [Full Text] [PDF]
|
|
|
|
|
|
C. Berry, R. Touyz, A. F. Dominiczak, R. C. Webb, and D. G. Johns Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2337 - H2365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. K BHATIA and D. O HASKARD Markers of inflammation in unstable angina Heart, June 1, 2001; 85(6): 603 - 604. [Full Text]
|
|
|
|
|
|
S. Wassmann, U. Laufs, A. T. Baumer, K. Muller, K. Ahlbory, W. Linz, G. Itter, R. Rosen, M. Bohm, and G. Nickenig HMG-CoA Reductase Inhibitors Improve Endothelial Dysfunction in Normocholesterolemic Hypertension via Reduced Production of Reactive Oxygen Species Hypertension, June 1, 2001; 37(6): 1450 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, J. Blanco, and J. Egido Systemic Infusion of Angiotensin II into Normal Rats Activates Nuclear Factor-{{kappa}}B and AP-1 in the Kidney : Role of AT1 and AT2 Receptors Am. J. Pathol., May 1, 2001; 158(5): 1743 - 1756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. Luft Workshop: Mechanisms and Cardiovascular Damage in Hypertension Hypertension, February 1, 2001; 37(2): 594 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Touyz and E. L. Schiffrin Signal Transduction Mechanisms Mediating the Physiological and Pathophysiological Actions of Angiotensin II in Vascular Smooth Muscle Cells Pharmacol. Rev., December 1, 2000; 52(4): 639 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Gosgnach, D. Messika-Zeitoun, W. Gonzalez, M. Philipe, and J.-B. Michel Shear stress induces iNOS expression in cultured smooth muscle cells: role of oxidative stress Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1880 - C1888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Gonzalez, V. Fontaine, M. E. Pueyo, N. Laquay, D. Messika-Zeitoun, M. Philippe, J.-F. Arnal, M.-P. Jacob, and J.-B. Michel Molecular Plasticity of Vascular Wall During NG-Nitro-L-Arginine Methyl Ester-Induced Hypertension : Modulation of Proinflammatory Signals Hypertension, July 1, 2000; 36(1): 103 - 109. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||