Published online before print August 26, 2002, doi: 10.1161/01.HYP.0000032031.30374.32
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(Hypertension. 2002;40:477.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Activation of NADPH Oxidase During Progression of Cardiac Hypertrophy to Failure
From the Department of Cardiology, Guy’s King’s & St Thomas’ School of Medicine (Denmark Hill Campus), King’s College London, London, United Kingdom.
Correspondence to Ajay M Shah MD, FRCP, Department of Cardiology, GKT School of Medicine (Denmark Hill Campus), Bessemer Road, London SE5 9PJ, United Kingdom. E-mail ajay.shah{at}kcl.ac.uk
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Abstract |
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Increased reactive oxygen species (ROS) production is implicated in the pathophysiology of left ventricular (LV) hypertrophy and heart failure. However, the enzymatic sources of myocardial ROS production are unclear. We examined the expression and activity of phagocyte-type NADPH oxidase in LV myocardium in an experimental guinea pig model of progressive pressure-overload LV hypertrophy. Concomitant with the development of LV hypertrophy, NADPH-dependent O2- production in LV homogenates, measured by lucigenin (5 µmol/L) chemiluminescence or cytochrome c reduction assays, significantly and progressively increased (by
40% at the stage of LV decompensation; P<0.05). O2- production was fully inhibited by diphenyleneiodonium (100 µmol/L). Immunoblotting revealed a progressive increase in expression of the NADPH oxidase subunits p22phox, gp91phox, p67phox, and p47phox in the LV hypertrophy group, whereas immunolabeling studies indicated the presence of oxidase subunits in cardiomyocytes and endothelial cells. In parallel with the increase in O2- production, there was a significant increase in activation of extracellular signal–regulated kinase 1/2, extracellular signal–regulated kinase 5, c-Jun NH2-terminal kinase 1/2, and p38 mitogen-activated protein kinase. These data indicate that an NADPH oxidase expressed in cardiomyocytes is a major source of ROS generation in pressure overload LV hypertrophy and may contribute to pathophysiological changes such as the activation of redox-sensitive kinases and progression to heart failure.
Key Words: hypertrophy • free radicals • heart failure • myocardium • reactive oxygen species
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Introduction |
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An increase in oxidative stress resulting from increased cardiac generation of reactive oxygen species (ROS) is implicated in the pathophysiology of pressure-overload left ventricular hypertrophy (LVH) and congestive heart failure, both experimentally and in clinical studies.1–3 Increased ROS production is implicated in the development of cellular hypertrophy and remodeling, at least in part through activation of redox-sensitive protein kinases such as the mitogen-activated protein kinase (MAPK) superfamily. The transition from compensated pressure-overload LVH to heart failure is associated with increased oxidative stress, which may promote myocyte apoptosis and necrosis. Several key proteins involved in excitation-contraction coupling, such as sarcolemmal ion channels and exchangers and sarcoplasmic reticulum calcium release channels, can undergo redox-sensitive alterations in activity, which contributes to myocardial contractile dysfunction. ROS also has indirect effects resulting from increased inactivation of NO and consequent generation of peroxynitrite, eg, coronary vascular endothelial dysfunction and peroxynitrite-induced inhibition of myocardial respiration.4
The sources of ROS generation that contribute to these effects in pressure-overload LVH and heart failure remain poorly defined. Potential sources include the mitochondrial electron transport chain, xanthine oxidase, cytochrome P450–based enzymes, dysfunctional NO synthases (NOSs), and infiltrating inflammatory cells such as neutrophils. Recently, a major source of ROS production in cardiovascular cells such as vascular smooth muscle, endothelium, and adventitial fibroblasts has been shown to be a phagocyte-type NADPH oxidase.5–8 The prototypic NADPH oxidase complex consists of a core heterodimer comprising 1 p22phox and 1 gp91phox subunit, and 4 regulatory subunits—p40phox, p47phox, p67phox, and rac1.9 In vascular smooth muscle, the gp91phox subunit is replaced by 1 of 2 homologs termed Nox1 and Nox4.5 The ROS-generating activity of vascular smooth muscle and endothelial NADPH oxidases is increased by stimuli such as angiotensin II, tumor necrosis factor-
, growth factors and cyclical load. Vascular NADPH oxidases are implicated in the development of angiotensin II–induced vascular smooth muscle hypertrophy, hypertension, endothelial dysfunction, and atherosclerosis.5
Whether a similar NADPH oxidase is expressed in the heart, particularly in cardiomyocytes, and whether it plays a role in the pathophysiology of LVH and heart failure have received little attention. Some studies have provided biochemical evidence for the presence of a phagocyte-type NADPH oxidase in cardiomyocytes, but the molecular nature of the enzyme was not addressed.10,11 Recently, we reported that experimental angiotensin II–induced cardiac hypertrophy was inhibited in gene-modified mice lacking the gp91phox subunit of NADPH oxidase.12 However, the response of NADPH oxidase to the more clinically relevant stimulus of chronic pressure overload is unknown. Furthermore, it is unclear what cardiac cell types the oxidase is expressed in or what changes occur in oxidase expression and activity during development of hypertrophy.
The aims of the present study were to investigate the following in an experimental model of progressive pressure-overload LVH: (1) whether alterations in expression and activity of NADPH oxidase contribute to increased ROS generation during progression to decompensated LVH and failure, (2) whether the oxidase is expressed in cardiomyocytes, and (3) the relationship between ROS generation and potential functional consequences such as activation of redox-sensitive MAPKs.
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Experimental Hypertrophy
All procedures were performed in accordance with the Guidance on the Operation of the Animals (Scientific Procedures) Act 1986 (Her Majesty’s Stationery Office, London, United Kingdom). Male Dunkin-Hartley guinea pigs (200 to 250 g; Harlan UK Ltd, Bicestor, UK) underwent suprarenal abdominal aortic banding or sham banding.13 Aortic banding in guinea pigs is a well-established model of pressure-overload LVH that has been preferred over small rodent models in several studies because guinea pig LV more closely resembles human myocardium with respect to myosin heavy-chain isoform expression and electrophysiological characteristics. In this model, compensated LVH is present from 2 weeks after surgery followed by a transition phase from 4 to 6 weeks and then overt LV decompensation at 8 to 10 weeks.13 Animals from the banded and sham groups were euthanized at 1, 3, 6, and 10 weeks postoperatively for harvesting of heart tissue. LV and right ventricular weights, lung weight, and body weight were determined, and tissue for immunoblotting, immunohistochemistry, or biochemistry was snap-frozen in liquid N2 and stored at -70°C until study.
Protein extraction and Immunoblotting
LV protein samples were prepared as described previously without Triton X-100.14 The antibodies against p22phox, CD31, phospho-extracellular signal–regulated kinase (ERK) 1/2, phospho–c-Jun NH2-terminal kinase (JNK), and ERK5 were from Santa Cruz Biotechnology; antibodies to gp91phox, p40phox, p47phox, and rac1 were kind gifts from Dr F Wientjes (University College London, United Kingdom); the monoclonal anti-p67phox was a kind gift from Dr M Quinn (Montana State University, Bozeman, Mont). Human neutrophil membrane protein (kindly provided by Dr F Wientjes) was the positive control for p22phox and gp91phox, and the protein extract from human phagocytic U937 cells after phorbol 12-myristate 13-acetate stimulation was the positive control for the other subunits. An anti-cardiac troponin I monoclonal antibody was kindly provided by Dr I Trayer (University of Birmingham, United Kingdom). The anti--tubulin monoclonal was from Sigma; and the anti-phospho-p38 MAPK antibody was from Cell Signaling Technology.
Immunohistochemistry
Samples were prepared as described previously.15 Frozen sections were first treated with a Biotin Blocking kit (DAKO) according to manufacturer instructions. Primary antibodies were used at 1:50 to 1:250 dilution in 0.1% BSA/PBS for 30 minutes at room temperature. Biotin-conjugated anti-rabbit, anti-goat, or anti-mouse IgG (1:500 dilution) was used as a secondary and was detected by a StreptABCcomplex/HRP kit (DAKO). For immunofluorescence staining, specific binding was detected by fluorescein isothiocyanate– or tetramethyl rhodamine isothiocyanate (TRITC)-labeled extravidin (green and red fluorescence, respectively). Normal rabbit or mouse IgG (5 µg/mL) was used instead of primary antibody as a negative control. Images were acquired on a Zeiss microscope coupled to a digital imaging system (Improvision, United Kingdom).
Lucigenin Chemiluminescence
O2-production by LV tissue homogenate (n=6 hearts per group at each time point) was measured using lucigenin-enhanced chemiluminescence in a microplate luminometer (Anthos Lucy 1, Austria).16 A low lucigenin concentration (5 µmol/L) was employed to minimize artifactual O2- production owing to redox cycling. Briefly, proteins were diluted in modified HEPES buffer and distributed (100 µg/well) onto a 96-well microplate. NADPH (100 µmol/L) and dark-adapted lucigenin were added to wells just before reading. O2- production was expressed as arbitrary light units over 20 minutes. Some experiments were performed in the presence of superoxide dismutase (SOD, 200 U/mL) or a cell-permeable superoxide scavenger, tiron (10 mmol/L). The following agents were used in some experiments to assess potential sources of O2- production: diphenyleneiodonium (100 µmol/L), a flavoprotein inhibitor that blocks NADPH oxidase; the NOS inhibitor NG-nitro-L-arginine methyl ester (100 µmol/L); an inhibitor of the mitochondrial electron chain, rotenone (50 µmol/L); or a xanthine oxidase inhibitor, oxypurinol (100 µmol/L). All studies were performed in triplicate.
Cytochrome c Reduction Assay
NADPH-dependent O2- production was also examined using SOD-inhibitable cytochrome c reduction.16 LV tissue homogenate (final concentration 1 mg/mL) diluted in Dulbecco’s modified Eagle’s medium without phenol red was distributed in 96-well plates (final volume, 200 µL/well). Cytochrome c (500 µmol/L) and NADPH (100 µmol/L) were added in the presence or absence of SOD (200 U/mL) and incubated at room temperature for 30 minutes. Cytochrome c reduction was measured by reading absorbance at 550 nm on a microplate reader.
Statistics
All data are presented as mean±SD from 
6 animals in each group at each time point after the operation (except anywhere mentioned in the text). Comparisons were made by unpaired t test, with Bonferonni correction for multiple testing, or by 1-way ANOVA as appropriate. P<0.05 was considered significant.
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Results |
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NADPH-Dependent ROS Generation During Progression of LVH
As reported previously,13 LV/body weight ratio was significantly higher by 3 weeks after surgery in the banded group compared with the sham group. Lung/body weight ratio was increased in the banded group by 10 weeks after surgery (Figure 1A and 1B). Body weights were similar in bands and shams at each stage (data not shown).
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NADPH-dependent O2- production by LV homogenates assessed by lucigenin chemiluminescence was significantly increased in the banded group by 3 weeks after surgery, concomitant with development of LVH, and had increased further by 6 weeks after surgery (Figure 1C). No further increase in ROS production was observed between 6 and 10 weeks.
Similar results were obtained with the cytochrome c reduction and lucigenin assays. Figure 2A shows a comparison of ROS production measured by cytochrome c reduction or lucigenin chemiluminescence at the 10-week stage.
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Enzymatic sources of NADPH-dependent ROS production were examined using specific inhibitors in the lucigenin assay. Figure 2B shows results for the 10-week stage (similar results were obtained at 3 and 6 weeks). ROS production was abolished either by tiron or diphenyleneiodonium, and was substantially reduced by SOD, both in the banded and sham groups. Rotenone and oxypurinol had no effect in either group. Interestingly, there was a slight (17±11%) but significant (P<0.05) reduction in NADPH-dependent ROS production in the presence of NG-nitro-L-arginine methyl ester in the banded group.
Protein Expression of NADPH Oxidase Subunits
LV tissue homogenates from the same hearts as used for measuring ROS production were used for immunoblotting. All 5 subunits of NADPH oxidase—ie, p22phox, gp91phox, p67phox, p47phox, p40phox, and rac1—were detectable in both groups using anti-human neutrophil antibodies (Figure 3). gp91phox in guinea pig LV tissue migrated as a band at 75 kDa and 2 bands of higher apparent molecular weight (mw) at 90 to 100 kDa, which was broadly similar to the pattern for neutrophil membrane protein. p47phox was detected as a doublet band, both in guinea pig myocardium and U937 cells. The expression of p22phox, gp91phox, p67phox, and p47phox became progressively higher in the LVH group compared with shams with increasing LVH (Figures 3 and 4). Interestingly, p22phox, gp91phox, and p67phox expression appeared to increase earlier than did p47phox, which did not increase until 6 weeks after surgery. The expression level of p40phox and rac1 was similar in the 2 groups.
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To assess which cell types in the heart expressed NADPH oxidase subunits, we undertook immunohistochemistry on LV sections from sham and LVH groups. Figure 5A shows the expression of gp91phox detected by peroxidase histostaining in sham (top) and LVH (middle) at 10 weeks after surgery. It is evident that gp91phox was expressed within the cardiac myocytes and that the level of expression was higher in LVH tissue compared with shams. Similar results were obtained with immunofluorescence staining (data not shown). p67phox and p47phox were also expressed in cardiomyocytes (data not shown). NADPH oxidase subunits were also expressed in endothelial cells, albeit at a lower level. Figure 5B shows LV sections double immunolabeled with a goat polyclonal anti-CD31 antibody as a specific endothelial cell marker17 (red fluorescence) and either a monoclonal anti-p67phox antibody (green fluorescence; Figure 5B, left) or a rabbit polyclonal anti-p22phox antibody (green fluorescence; Figure 5B, right). Superimposition of the images indicates that p67phox and p22phox were expressed both in coronary endothelium and cardiomyocytes.
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Changes in Expression and Phosphorylation of p38-MAPK, ERK1/2, JNK, and ERK5 During the Development of LVH and Heart Failure
To investigate the possible relationship between NADPH oxidase activation and the activation of redox-sensitive kinases, we measured the phosphorylation of ERK1/2, p38-MAPK, JNK, and ERK5 (Figure 6). The levels of phosphorylated ERK1/2 increased significantly in LV myocardium of the banded group compared with shams by 3 weeks after surgery and continued to increase further with progression of LVH and heart failure. The expression of ERK5 and phospho-p38 MAPK was significantly increased in LVH samples at 6 and 10 weeks after surgery. The levels of phosphorylated JNK increased significantly during the early stages of LVH but declined during the phase of LV decompensation (10 weeks).
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Discussion |
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The major findings of the present study are that (1) all the main components of a functional phagocyte-type NADPH oxidase are expressed in guinea pig myocardium, notably in cardiomyocytes; (2) NADPH oxidase–derived ROS generation increases significantly in pressure overload LVH, at least partly as a result of increased expression of oxidase components; and (3) the increase in myocardial NADPH oxidase activity is paralleled by activation of the redox-sensitive kinases ERK1/2, ERK5, and p38 MAPK and by progression of cardiac hypertrophy. Collectively, these findings suggest that NADPH oxidase activation may play an important pathophysiological role in progressive pressure-overload LVH and heart failure.
Although a phagocyte-type NADPH oxidase has been demonstrated in many cardiovascular cell types,5–8 previous data for its expression in cardiomyocytes were mainly biochemical.10,11 In a recent study, cardiac mRNA expression of p22phox and gp91phox was reportedly increased after myocardial infarction; however, this was probably related to increased neutrophil infiltration, whereas evidence of cardiomyocyte expression was not reported.18 In the current study, we show that all the main subunits of the phagocyte-type NADPH oxidase (including gp91phox) are expressed at protein level in guinea pig myocardium, and that the cell types in which the oxidase is expressed include the cardiomyocyte.
Although increased ROS production during progressive pressure-overload LVH is well recognized, the sources of these ROS have been unclear. In this study, we clearly demonstrated that a phagocyte-type NADPH oxidase was a major ROS source. Interestingly, a small but significant proportion (17%) of NADPH-dependent ROS production could be inhibited by an NOS inhibitor, suggesting that dysfunctional NOS activity may also partly contribute to ROS production.19 This is not surprising because it has been suggested that ROS production from any source may induce dysfunctional O2--generating NOS activity, as a consequence of ROS-dependent degradation of the essential NOS cofactor tetrahydrobiopterin.20 Potential mechanisms through which NADPH oxidase activity is increased include transcriptional upregulation of oxidase components and posttranslational modifications, such as p47phox phosphorylation and rac1 translocation.9 In the present study, at least part of the mechanism underlying the increased NADPH oxidase activity was an increase in expression of p22phox, gp91phox, p67phox, and p47phox. Stimuli that augment NADPH oxidase activity in the peripheral vasculature and may be relevant to pressure-overload LVH include angiotensin II, tumor necrosis factor-, and mechanical stretch.5 The relative contribution of these stimuli to the upregulation observed in the present study requires further investigation.
An increase in ROS production may have several potential effects in the hypertrophying heart. In isolated cardiomyocytes, a moderate increase in ROS induces hypertrophy and apoptosis.21 Angiotensin II– and tumor necrosis factor-–induced hypertrophy of cultured cardiomyocytes is abrogated by antioxidants.22,23 Recently, we reported that angiotensin II induced in vivo cardiac hypertrophy was inhibited in gp91phox-null mice.12 The mitogenic effects of ROS may involve modulation of redox-sensitive signaling pathways such as Src kinases and MAPKs (including ERK1/2, ERK5, and p38 MAPK), which leads to activation of transcriptional factors.3,24,25 The subsequent changes in gene expression may account for many of the changes in LVH. Activation of redox-sensitive signaling pathways may also be implicated in the transition of compensated LVH to heart failure. In the present study, increased myocardial NADPH oxidase activity was accompanied by activation of ERK1/2, ERK5, and p38 MAPK. ERK1/2 has been implicated in cardiac hypertrophy,3,25–27 being induced by increased pressure28 and Gq-coupled receptor agonists.29 ERK1/2 and ERK5 are significantly activated by H2O2 perfusion in the isolated guinea pig heart.30 Although many studies have proposed that ROS mediates cardiomyocyte hypertrophic response to agonist stimulation via the ERK cascade,3,26,27 the mechanisms that couple hypertrophic signals to activation of ERK signaling and gene expression remain unclear. The current results suggest that agonist-induced activation of NADPH oxidase may be an important upstream component of the pathway leading to activation of redox-sensitive MAPKs such as ERK1/2 and ERK5. Interestingly, in the present study, ERK1/2 activation was observed quite early at the stage of compensated LVH, whereas activation of p38 MAPK and ERK5 occurred at the transition stage between compensated and decompensated LVH. This could reflect a differential involvement of these kinases in hypertrophy versus transition to heart failure.31 In addition, we found that while activation of JNK was observed early during LVH, during the development of failure the levels of phospho-JNK declined despite maintained NADPH oxidase activity. This finding suggests dissociation between NADPH oxidase–derived ROS production and the activation of specific MAPKs.
Another important consequence of increased ROS production is endothelial dysfunction resulting from increased inactivation of NO.19 It is of interest that we found NADPH oxidase expression not only in cardiomyocytes but also in coronary microvascular endothelium. Indeed, it is well recognized that endothelial cells express NADPH oxidase and produce O2-,5–7,19,32 and we have recently reported that increased endothelial ROS production may contribute to impaired LV relaxation in pressure-overload LVH.33
Perspectives
This is the first study to report a progressive activation of NADPH oxidase in the myocardium in pressure overload LVH and suggests that this enzyme system may play a role in myocardial pathophysiology analogous to reports of its importance in the vasculature. NADPH oxidase–derived ROS may potentially contribute to several aspects of the pathophysiology of LVH and heart failure. In particular, activation of redox-sensitive signaling molecules such as ERK1/2, ERK5, and p38 MAPK may be involved in the development of hypertrophy and/or transition to heart failure.
To define the precise contribution of NADPH oxidase-derived in LVH and the mechanisms underlying upregulation of NADPH oxidase activity after imposition of pressure overload, it will be necessary to undertake appropriate studies in experimental models, including gene-modified animals. The possibility that targeting myocardial NADPH oxidase expression and activity may provide a means of modifying development of LVH and heart failure merits investigation.
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Acknowledgments |
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This work was supported by British Heart Foundation (BHF) program grant RG/98008. N.P.G. was supported by a BHF Junior Fellowship. A.M.S. holds the BHF Chair of Cardiology in King’s College London.
Received May 17, 2002; first decision June 7, 2002; accepted July 23, 2002.
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References |
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|---|
1. Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens. 2000; 18: 655–673.[CrossRef][Medline] [Order article via Infotrieve]
2. Chien KR. Stress pathways and heart failure. Cell. 1999; 98: 555–558.[CrossRef][Medline] [Order article via Infotrieve]
3. Sugden PH, Clerk A. Cellular mechanisms of cardiac hypertrophy. J Mol Med. 1998; 76: 725–746.[CrossRef][Medline] [Order article via Infotrieve]
4. Shah AM, MacCarthy PA. Paracrine and autocrine effects of nitric oxide on myocardial function. Pharmacol Ther. 2000; 86: 49–86.[CrossRef][Medline] [Order article via Infotrieve]
5. Griendling KK, Sorescu D, Ushio-Fukai M, NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000; 86: 494–501.
6. Bayraktutan U, Blayney L, Shah AM. Molecular characterization and localization of the NAD(P)H oxidase components gp91-phox and p22-phox in endothelial cells. Arterioscl Thromb Vasc Biol. 2000; 20: 1903–1911.
7. Gorlach A, Brandes RP, Nguyen K, Amidi M, Dehghani F, Busse R. A gp-91-phox containing NADPH oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall. Circ Res. 2000; 87: 26–32.
8. Pagano PJ, Clark JK, Cifuentes-Pagano ME, Clark SM, Callis GM, Quinn MT. Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: enhancement by angiotensin II. Proc Natl Acad Sci U S A. 1997; 94: 14483–14488.
9. Babior BM. NADPH oxidase: an update. Blood. 1999; 93: 1464–1476.
10. Mohazzab-H KM, Kaminaki PM, Wolin MS. Lactate and PO2 modulate superoxide anion production in bovine cardiac myocytes. Circulation. 1997; 96: 614–620.
11. Souren JEM, Van Der Mast C, van Zwieten R. NADPH-oxidase–dependent superoxide production by myocyte-derived H9c2 cells: influence of ischemia, heat shock, cycloheximide and cytochalasin D. J Mol Cell Cardiol. 1997; 29: 2803–2812.[CrossRef][Medline] [Order article via Infotrieve]
12. Bendall JK, Cave AC, Heymes C, Gall N, Shah AM. Pivotal role of gp91phox-containing NADPH oxidase in angiotensin II–induced cardiac hypertrophy in mice. Circulation. 2002; 2002: 105: 293–296.
13. Grieve DJ, MacCarthy PA, Gall NP, Cave AC, Shah AM. Divergent biological actions of coronary endothelial nitric oxide during progression of cardiac hypertrophy. Hypertension. 2001; 38: 267–273.
14. Li J-M, Poolman RA, Brooks G. Role of G1 phase cyclins and cyclin-dependent kinases during cardiomyocyte hypertrophic growth in rats. Am J Physiol. 1998; 275: H814–H822.[Medline] [Order article via Infotrieve]
15. Li J-M, Brooks G. Differential protein expression and subcellular distribution of TGFß1, ß2 and ß3 in cardiomyocytes during pressure overload-induced hypertrophy. J Mol Cell Cardiol. 1997; 29: 2213–2224.[CrossRef][Medline] [Order article via Infotrieve]
16. Li J-M, Mullen AM, Yun S, Wientjes F, Brouns GY, Thrasher AJ, Shah AM. Essential role of the NADPH oxidase subunit p47phox in endothelial cell superoxide production in response to phorbol ester and tumor necrosis factor-. Circ Res. 2002; 90: 143–150.
17. Albelda SM, Muller WA, Buck CA, Newman PJ. Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule. J Cell Biol. 1991; 14: 1059–1068.
18. Fukui T, Yoshiyama M, Hanatani A, Omura T, Yoshikawa J, Abe Y. Expression of p22-phox and gp91-phox, essential components of NADPH oxidase, increases after myocardial infarction. Biochem Biophys Res Commun. 2001; 281: 1200–1206.[CrossRef][Medline] [Order article via Infotrieve]
19. Harrison DG. Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest. 1997; 100: 2153–2157.[Medline] [Order article via Infotrieve]
20. Laursen JB, Somers M, Kurz S, McCann L, Warnholtz A, Freeman BA, Tarpey M, Fukai T, Harrison DG. Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation. 2001; 103: 1282–1288.
21. Siwik DA, Tzortzis JD, Pimental DR, Chang DL-F, Pagano PJ, Singh K, Sawyer DB, Colucci WS. Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro. Circ Res. 1999; 85: 147–153.
22. Nakamura K, Fushimi K, Kouchi H, Mihara K, Miyazaki M, Ohe T, Namba M. Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor- and angiotensin II. Circulation. 1998; 98: 794–799.
23. Wenzel S, Taimor G, Piper HM, Schlüeter K-D. Redox-sensitive intermediates mediate angiotensin II–induced p38 MAP kinase activation, AP-1 binding activity, and TGF-ß expression in adult ventricular cardiomyocytes. FASEB J. 2001; 10: 2291–2293.
24. Kunsch C, Medford RM. Oxidative stress as a regulator of gene expression in the vasculature. Circ Res. 1999; 85: 753–766.
25. Tanaka K, Honda M, Takabatake T. Redox regulation of MAPK pathway and cardiac hypertrophy in adult rat cardiac myocyte. J Am Coll Cardiol. 2001; 37: 676–685.
26. Yue T-L, Gu J-L, Wang C, Reith AD, Lee JC, Mirabile RC, Kreutz R, Wang Y, Maleeff B, Parsons AA, Ohlstein EH. Extracellular signal–regulated kinase plays an essential role in hypertrophic agonists, endothelin-1 and phenylephrine-induced cardiomyocyte hypertrophy. J Biol Chem. 2000; 275: 37895–37901.
27. Shih N-L, Cheng T-H, Loh S-H, Cheng P-Y, Wang DL, Chen Y-S, Liu S-H, Liew C-C, Chen J-J. Reactive oxygen species modulate angiotensin II–induced ß-myosin heavy chain gene expression via ras/raf/extracellular signal–regulated kinase pathway in neonatal rat cardiomyocytes. Biochem Biophys Res Commun. 2001; 283: 143–148.[CrossRef][Medline] [Order article via Infotrieve]
28. Birukov KG, Lehoux S, Birukova AA, Merval R, Tkachuk VA, Tedgui A. Increased pressure induced sustained protein kinase C–independent hybrimycin A–sensitive activation of extracellular signal–related kinase 1/2 in the rabbit aorta in organ culture. Circ Res. 1997; 81: 895–903.
29. Esposito G, Naga Prasad SV, Rapacciuolo A, Mao L, Koch WJ, Rockman HA. Cardiac overexpression of a Gq inhibitor blocks induction of extracellular signal–regulated kinase and c-Jun NH2-terminal kinase activity in in vivo pressure overload. Circulation. 2001; 103: 1453–1458.
30. Takeishi Y, Abe J-I, Lee JD, Kawakatsu H, Walsh R, Berk BC. Differential regulation of p90 ribosomal S6 kinase and big mitogen-activated protein kinase by ischemia/reperfusion and oxidative stress in perfused guinea pig hearts. Circ Res. 1999; 85: 1164–1172.
31. Wang Y, Huang S, Sah VP, Ross Jr J, Brown JH, Han J, Chien KR. Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen–activated protein kinase family. J Biol Chem. 1998; 273: 2161–2168.
32. Lang D, Mosfer SI, Shakesby A, Donaldson F, Lewis MJ. Coronary microvascular endothelial cell redox state in left ventricular hypertrophy. Circ Res. 2000; 86: 463–469.
33. MacCarthy PA, Grieve DG, Li J-M, Dunster C, Kelly FJ, Shah AM. Impaired endothelial regulation of ventricular relaxation in cardiac hypertrophy: role of reactive oxygen species and NADPH oxidase. Circulation. 2001; 104: 2967–2974.
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T. Tsutsumi, T. Ide, M. Yamato, W. Kudou, M. Andou, Y. Hirooka, H. Utsumi, H. Tsutsui, and K. Sunagawa Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction Cardiovasc Res, March 1, 2008; 77(4): 713 - 721. [Abstract] [Full Text] [PDF]
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 Y. H. Looi, D. J. Grieve, A. Siva, S. J. Walker, N. Anilkumar, A. C. Cave, M. Marber, M. J. Monaghan, and A. M. Shah Involvement of Nox2 NADPH Oxidase in Adverse Cardiac Remodeling After Myocardial Infarction Hypertension, February 1, 2008; 51(2): 319 - 325. [Abstract] [Full Text] [PDF]
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G. Sanchez, M. Escobar, Z. Pedrozo, P. Macho, R. Domenech, S. Hartel, C. Hidalgo, and P. Donoso Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible role in cardioprotection Cardiovasc Res, January 15, 2008; 77(2): 380 - 386. [Abstract] [Full Text] [PDF]
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 A. R. Hemnes, A. Zaiman, and H. C. Champion PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L24 - L33. [Abstract] [Full Text] [PDF]
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Z. Ren, F. J. Raucci Jr., D. M. Browe, and C. M. Baumgarten Regulation of swelling-activated Cl- current by angiotensin II signalling and NADPH oxidase in rabbit ventricle Cardiovasc Res, January 1, 2008; 77(1): 73 - 80. [Abstract] [Full Text] [PDF]
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E. M. Redout, M. J. Wagner, M. J. Zuidwijk, C. Boer, R. J.P. Musters, C. van Hardeveld, W. J. Paulus, and W. S. Simonides Right-ventricular failure is associated with increased mitochondrial complex II activity and production of reactive oxygen species Cardiovasc Res, September 1, 2007; 75(4): 770 - 781. [Abstract] [Full Text] [PDF]
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T. Yamashita, E. Yamamoto, K. Kataoka, T. Nakamura, S. Matsuba, Y. Tokutomi, Y.-F. Dong, H. Ichijo, H. Ogawa, and S. Kim-Mitsuyama Apoptosis Signal-Regulating Kinase-1 Is Involved in Vascular Endothelial and Cardiac Remodeling Caused by Nitric Oxide Deficiency Hypertension, September 1, 2007; 50(3): 519 - 524. [Abstract] [Full Text] [PDF]
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 S. Stas, A. Whaley-Connell, J. Habibi, L. Appesh, M. R. Hayden, P. R. Karuparthi, M. Qazi, E. M. Morris, S. A. Cooper, C. D. Link, et al. Mineralocorticoid Receptor Blockade Attenuates Chronic Overexpression of the Renin-Angiotensin-Aldosterone System Stimulation of Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Cardiac Remodeling Endocrinology, August 1, 2007; 148(8): 3773 - 3780. [Abstract] [Full Text] [PDF]
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 M. Seddon, Y. H Looi, and A. M Shah Oxidative stress and redox signalling in cardiac hypertrophy and heart failure Heart, August 1, 2007; 93(8): 903 - 907. [Abstract] [Full Text] [PDF]
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A. Muthumala, H. Montgomery, J. Palmen, J. A. Cooper, and S. E. Humphries Angiotensin-Converting Enzyme Genotype Interacts With Systolic Blood Pressure to Determine Coronary Heart Disease Risk in Healthy Middle-Aged Men Hypertension, August 1, 2007; 50(2): 348 - 353. [Abstract] [Full Text] [PDF]
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M. Kajiya, M. Hirota, Y. Inai, T. Kiyooka, T. Morimoto, T. Iwasaki, K. Endo, S. Mohri, J. Shimizu, T. Yada, et al. Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2737 - H2744. [Abstract] [Full Text] [PDF]
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 B. Angermayr, M. Fernandez, M. Mejias, J. Gracia-Sancho, J. C. Garcia-Pagan, and J. Bosch NAD(P)H oxidase modulates angiogenesis and the development of portosystemic collaterals and splanchnic hyperaemia in portal hypertensive rats Gut, April 1, 2007; 56(4): 560 - 564. [Abstract] [Full Text] [PDF]
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Z. Guo, Z. Xia, J. Jiang, and J. H. McNeill Downregulation of NADPH oxidase, antioxidant enzymes, and inflammatory markers in the heart of streptozotocin-induced diabetic rats by N-acetyl-L-cysteine Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1728 - H1736. [Abstract] [Full Text] [PDF]
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 C. Doerries, K. Grote, D. Hilfiker-Kleiner, M. Luchtefeld, A. Schaefer, S. M. Holland, S. Sorrentino, C. Manes, B. Schieffer, H. Drexler, et al. Critical Role of the NAD(P)H Oxidase Subunit p47phox for Left Ventricular Remodeling/Dysfunction and Survival After Myocardial Infarction Circ. Res., March 30, 2007; 100(6): 894 - 903. [Abstract] [Full Text] [PDF]
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 M. Buggisch, B. Ateghang, C. Ruhe, C. Strobel, S. Lange, M. Wartenberg, and H. Sauer Stimulation of ES-cell-derived cardiomyogenesis and neonatal cardiac cell proliferation by reactive oxygen species and NADPH oxidase J. Cell Sci., March 1, 2007; 120(5): 885 - 894. [Abstract] [Full Text] [PDF]
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E. Takimoto and D. A. Kass Role of Oxidative Stress in Cardiac Hypertrophy and Remodeling Hypertension, February 1, 2007; 49(2): 241 - 248. [Full Text] [PDF]
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I. Papparella, G. Ceolotto, L. Berto, M. Cavalli, S. Bova, G. Cargnelli, E. Ruga, O. Milanesi, L. Franco, M. Mazzoni, et al. Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat Cardiovasc Res, January 15, 2007; 73(2): 432 - 438. [Abstract] [Full Text] [PDF]
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 K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]
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 J. M. Zimmet and J. M. Hare Nitroso-Redox Interactions in the Cardiovascular System Circulation, October 3, 2006; 114(14): 1531 - 1544. [Full Text] [PDF]
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 S. D. Hingtgen, X. Tian, J. Yang, S. M. Dunlay, A. S. Peek, Y. Wu, R. V. Sharma, J. F. Engelhardt, and R. L. Davisson Nox2-containing NADPH oxidase and Akt activation play a key role in angiotensin II-induced cardiomyocyte hypertrophy Physiol Genomics, September 14, 2006; 26(3): 180 - 191. [Abstract] [Full Text] [PDF]
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H. Matsui, T. Shimosawa, Y. Uetake, H. Wang, S. Ogura, T. Kaneko, J. Liu, K. Ando, and T. Fujita Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction: Association With Reactive Oxygen Species Reduction Hypertension, August 1, 2006; 48(2): 225 - 231. [Abstract] [Full Text] [PDF]
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C. E. Murdoch, M. Zhang, A. C. Cave, and A. M. Shah NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure Cardiovasc Res, July 15, 2006; 71(2): 208 - 215. [Abstract] [Full Text] [PDF]
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F. Custodis, M. Eberl, H. Kilter, M. Bohm, and U. Laufs Association of RhoGDI{alpha} with Rac1 GTPase mediates free radical production during myocardial hypertrophy Cardiovasc Res, July 15, 2006; 71(2): 342 - 351. [Abstract] [Full Text] [PDF]
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Y. Liao, S. Takashima, H. Zhao, Y. Asano, Y. Shintani, T. Minamino, J. Kim, M. Fujita, M. Hori, and M. Kitakaze Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice Cardiovasc Res, April 1, 2006; 70(1): 107 - 116. [Abstract] [Full Text] [PDF]
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K. Nagata, K. Obata, J. Xu, S. Ichihara, A. Noda, H. Kimata, T. Kato, H. Izawa, T. Murohara, and M. Yokota Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Failure in Low-Aldosterone Hypertensive Rats Hypertension, April 1, 2006; 47(4): 656 - 664. [Abstract] [Full Text] [PDF]
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 D. M. Browe and C. M. Baumgarten EGFR Kinase Regulates Volume-sensitive Chloride Current Elicited by Integrin Stretch via PI-3K and NADPH Oxidase in Ventricular Myocytes J. Gen. Physiol., February 27, 2006; 127(3): 237 - 251. [Abstract] [Full Text] [PDF]
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 D. J. Grieve, J. A. Byrne, A. Siva, J. Layland, S. Johar, A. C. Cave, and A. M. Shah Involvement of the Nicotinamide Adenosine Dinucleotide Phosphate Oxidase Isoform Nox2 in Cardiac Contractile Dysfunction Occurring in Response to Pressure Overload J. Am. Coll. Cardiol., February 21, 2006; 47(4): 817 - 826. [Abstract] [Full Text] [PDF]
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 A. Cave, D. Grieve, S. Johar, M. Zhang, and A. M Shah NADPH oxidase-derived reactive oxygen species in cardiac pathophysiology Phil Trans R Soc B, December 29, 2005; 360(1464): 2327 - 2334. [Abstract] [Full Text] [PDF]
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D. Dawson, C. A. Lygate, M.-H. Zhang, K. Hulbert, S. Neubauer, and B. Casadei nNOS Gene Deletion Exacerbates Pathological Left Ventricular Remodeling and Functional Deterioration After Myocardial Infarction Circulation, December 13, 2005; 112(24): 3729 - 3737. [Abstract] [Full Text] [PDF]
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R. M. Saraiva, K. M. Minhas, S. V.Y. Raju, L. A. Barouch, E. Pitz, K. H. Schuleri, K. Vandegaer, D. Li, and J. M. Hare Deficiency of Neuronal Nitric Oxide Synthase Increases Mortality and Cardiac Remodeling After Myocardial Infarction: Role of Nitroso-Redox Equilibrium Circulation, November 29, 2005; 112(22): 3415 - 3422. [Abstract] [Full Text] [PDF]
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 A. K. Lund, S. L. Peterson, G. S. Timmins, and M. K. Walker Endothelin-1-Mediated Increase in Reactive Oxygen Species and NADPH Oxidase Activity in Hearts of Aryl Hydrocarbon Receptor (AhR) Null Mice Toxicol. Sci., November 1, 2005; 88(1): 265 - 273. [Abstract] [Full Text] [PDF]
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 S. Ikeda, M. Yamaoka-Tojo, L. Hilenski, N. A. Patrushev, G. M. Anwar, M. T. Quinn, and M. Ushio-Fukai IQGAP1 Regulates Reactive Oxygen Species-Dependent Endothelial Cell Migration Through Interacting With Nox2 Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2295 - 2300. [Abstract] [Full Text] [PDF]
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I. Cucoranu, R. Clempus, A. Dikalova, P. J. Phelan, S. Ariyan, S. Dikalov, and D. Sorescu NAD(P)H Oxidase 4 Mediates Transforming Growth Factor-{beta}1-Induced Differentiation of Cardiac Fibroblasts Into Myofibroblasts Circ. Res., October 28, 2005; 97(9): 900 - 907. [Abstract] [Full Text] [PDF]
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 H. CY, M. CE, D. J, G. AS, I. C, T. E, C. HC, L. M, R. S, R. ER, et al. Which Comes First--Renal Dysfunction or High Blood Pressure?: Elevated Blood Pressure and Risk of End-Stage Renal Disease in Subjects without Baseline Kidney Disease. Arch Intern Med 165: 923-928, 2005 J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2817 - 2820. [Full Text] [PDF]
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Y. M. Kim, T. J. Guzik, Y. H. Zhang, M. H. Zhang, H. Kattach, C. Ratnatunga, R. Pillai, K. M. Channon, and B. Casadei A Myocardial Nox2 Containing NAD(P)H Oxidase Contributes to Oxidative Stress in Human Atrial Fibrillation Circ. Res., September 30, 2005; 97(7): 629 - 636. [Abstract] [Full Text] [PDF]
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L. C. Hool, C. A. Di Maria, H. M. Viola, and P. G. Arthur Role of NAD(P)H oxidase in the regulation of cardiac L-type Ca2+ channel function during acute hypoxia Cardiovasc Res, September 1, 2005; 67(4): 624 - 635. [Abstract] [Full Text] [PDF]
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S. Kinugawa, J. Zhang, E. Messina, E. Walsh, H. Huang, P. M. Kaminski, M. S. Wolin, and T. H. Hintze gp91phox-containing NAD(P)H oxidase mediates attenuation of nitric oxide-dependent control of myocardial oxygen consumption by ANG II Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H862 - H867. [Abstract] [Full Text] [PDF]
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J. S. Becker, A. Adler, A. Schneeberger, H. Huang, Z. Wang, E. Walsh, A. Koller, and T. H. Hintze Hyperhomocysteinemia, a Cardiac Metabolic Disease: Role of Nitric Oxide and the p22phox Subunit of NADPH Oxidase Circulation, April 26, 2005; 111(16): 2112 - 2118. [Abstract] [Full Text] [PDF]
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T. Peng, X. Lu, and Q. Feng Pivotal Role of gp91phox-Containing NADH Oxidase in Lipopolysaccharide-Induced Tumor Necrosis Factor-{alpha} Expression and Myocardial Depression Circulation, April 5, 2005; 111(13): 1637 - 1644. [Abstract] [Full Text] [PDF]
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C. Sun, K. W. Sellers, C. Sumners, and M. K. Raizada NAD(P)H Oxidase Inhibition Attenuates Neuronal Chronotropic Actions of Angiotensin II Circ. Res., April 1, 2005; 96(6): 659 - 666. [Abstract] [Full Text] [PDF]
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A. Planavila, R. Rodriguez-Calvo, M. Jove, L. Michalik, W. Wahli, J. C. Laguna, and M. Vazquez-Carrera Peroxisome proliferator-activated receptor {beta}/{delta} activation inhibits hypertrophy in neonatal rat cardiomyocytes Cardiovasc Res, March 1, 2005; 65(4): 832 - 841. [Abstract] [Full Text] [PDF]
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N. R. Madamanchi, A. Vendrov, and M. S. Runge Oxidative Stress and Vascular Disease Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 29 - 38. [Abstract] [Full Text] [PDF]
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Y. Chen, M. Hou, Y. Li, J. H. Traverse, P. Zhang, D. Salvemini, T. Fukai, and R. J. Bache Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H133 - H141. [Abstract] [Full Text] [PDF]
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S. A. Gupte, P. M. Kaminski, B. Floyd, R. Agarwal, N. Ali, M. Ahmad, J. Edwards, and M. S. Wolin Cytosolic NADPH may regulate differences in basal Nox oxidase-derived superoxide generation in bovine coronary and pulmonary arteries Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H13 - H21. [Abstract] [Full Text] [PDF]
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 Y. Kuramochi, G. M. Cote, X. Guo, N. K. Lebrasseur, L. Cui, R. Liao, and D. B. Sawyer Cardiac Endothelial Cells Regulate Reactive Oxygen Species-induced Cardiomyocyte Apoptosis through Neuregulin-1{beta}/erbB4 Signaling J. Biol. Chem., December 3, 2004; 279(49): 51141 - 51147. [Abstract] [Full Text] [PDF]
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 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]
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D. M. Browe and C. M. Baumgarten Angiotensin II (AT1) Receptors and NADPH Oxidase Regulate Cl- Current Elicited by {beta}1 Integrin Stretch in Rabbit Ventricular Myocytes J. Gen. Physiol., August 30, 2004; 124(3): 273 - 287. [Abstract] [Full Text] [PDF]
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K K Griendling Novel NAD(P)H oxidases in the cardiovascular system Heart, May 1, 2004; 90(5): 491 - 493. [Full Text] [PDF]
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W. Nadruz Jr, V. J. Lagosta, H. Moreno Jr, O. R. Coelho, and K. G. Franchini Simvastatin Prevents Load-Induced Protein Tyrosine Nitration in Overloaded Hearts Hypertension, May 1, 2004; 43(5): 1060 - 1066. [Abstract] [Full Text] [PDF]
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J.-M. Li, S. Wheatcroft, L. M. Fan, M. T. Kearney, and A. M. Shah Opposing Roles of p47phox in Basal Versus Angiotensin II-Stimulated Alterations in Vascular O2- Production, Vascular Tone, and Mitogen-Activated Protein Kinase Activation Circulation, March 16, 2004; 109(10): 1307 - 1313. [Abstract] [Full Text] [PDF]
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M. Maytin, D. A. Siwik, M. Ito, L. Xiao, D. B. Sawyer, R. Liao, and W. S. Colucci Pressure Overload-Induced Myocardial Hypertrophy in Mice Does Not Require gp91phox Circulation, March 9, 2004; 109(9): 1168 - 1171. [Abstract] [Full Text] [PDF]
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 M. P. Czubryt and E. N. Olson Balancing Contractility and Energy Production: The Role of Myocyte Enhancer Factor 2 (MEF2) in Cardiac Hypertrophy Recent Prog. Horm. Res., January 1, 2004; 59(1): 105 - 124. [Abstract] [Full Text]
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 D. J Grieve and A. M Shah Oxidative stress in heart failure: More than just damage Eur. Heart J., December 2, 2003; 24(24): 2161 - 2163. [Full Text] [PDF]
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J. A. Byrne,*, D. J. Grieve, J. K. Bendall, J.-M. Li, C. Gove, J. D. Lambeth, A. C. Cave, and A. M. Shah Contrasting Roles of NADPH Oxidase Isoforms in Pressure-Overload Versus Angiotensin II-Induced Cardiac Hypertrophy Circ. Res., October 31, 2003; 93(9): 802 - 805. [Abstract] [Full Text] [PDF]
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F. Moritz, C. Monteil, M. Isabelle, F. Bauer, S. Renet, P. Mulder, V. Richard, and C. Thuillez Role of reactive oxygen species in cocaine-induced cardiac dysfunction Cardiovasc Res, October 1, 2003; 59(4): 834 - 843. [Abstract] [Full Text] [PDF]
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C. Maack, T. Kartes, H. Kilter, H.-J. Schafers, G. Nickenig, M. Bohm, and U. Laufs Oxygen Free Radical Release in Human Failing Myocardium Is Associated With Increased Activity of Rac1-GTPase and Represents a Target for Statin Treatment Circulation, September 30, 2003; 108(13): 1567 - 1574. [Abstract] [Full Text] [PDF]
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J.-M. Li and A. M. Shah ROS Generation by Nonphagocytic NADPH Oxidase: Potential Relevance in Diabetic Nephropathy J. Am. Soc. Nephrol., August 1, 2003; 14(90003): S221 - 226. [Abstract] [Full Text] [PDF]
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C. Heymes, J. K. Bendall, P. Ratajczak, A. C. Cave, J.-L. Samuel, G. Hasenfuss, and A. M. Shah Increased myocardial NADPH oxidase activity in human heart failure J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2164 - 2171. [Abstract] [Full Text] [PDF]
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A. Warnholtz and T. Munzel The failing human heart: Another battlefield for the NAD(P)H oxidase? J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2172 - 2174. [Full Text] [PDF]
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A. Sachinidis, B. K. Fleischmann, E. Kolossov, M. Wartenberg, H. Sauer, and J. Hescheler Cardiac specific differentiation of mouse embryonic stem cells Cardiovasc Res, May 1, 2003; 58(2): 278 - 291. [Abstract] [Full Text] [PDF]
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