Celecoxib modulates hypertrophic signalling and prevents load‐induced cardiac dysfunction

Jacobshagen, Claudius; Grüber, Meike; Teucher, Nils; Schmidt, Albrecht; Unsöld, Bernhard; Toischer, Karl; Van, Phuc Nguyen; Maier, Lars S.; Kögler, Harald; Hasenfuß, Gerd

doi:10.1016/j.ejheart.2008.02.013

Cited by 20 publications

(11 citation statements)

References 53 publications

(88 reference statements)

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“…In male C57BL/6J mice subjected to TAC with a 27 gauge sizing needle, mortality rates <25% (16,19,25-27), 25-50% (18,20,28-30), 50-75% (31,32), or greater than 75% (8,33) have been reported although many studies do not report mortality. Similarly, in male C57/BL6 mice subjected to TAC with a 27 gauge sizing needle, reported increments in LV mass over SHAM vary from 28% to 130% at 3 weeks (15,24), and from 58% to 190% at 7-9 weeks (34,35).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, in male C57/BL6 mice subjected to TAC with a 27 gauge sizing needle, reported increments in LV mass over SHAM vary from 28% to 130% at 3 weeks (15,24), and from 58% to 190% at 7-9 weeks (34,35). Studies using male C57BL/6J mice subjected to TAC with a 27 gauge sizing needle have also varied in characterizing TAC as a model of HF (6-8,10) vs compensated LVH (2-5). These differences are consistent with the variability we observed studying a large number of consecutive mice subjected to TAC with a 27 gauge sizing needle.…”

Section: Discussionmentioning

confidence: 99%

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Variable phenotype in murine transverse aortic constriction

Mohammed

Storlie

Oehler

et al. 2012

Cardiovascular Pathology

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Background In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload induced hypertrophy (LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, non-invasive method of prospectively identifying mice with HF versus compensated LVH after TAC. Methods Eight week old, male C57BL/6J mice underwent TAC or SHAM and then echo at three weeks post-TAC. A group of SHAM and TAC mice were sacrificed after the three week echocardiogram, while the remainder underwent repeat echo and sacrifice at nine weeks post-TAC. The presence of TAC was assessed with 2 dimensional echo, anatomic aortic m-mode and color flow and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset. HF was defined as lung/body weight > upper limit in SHAM operated mice. Results As compared to SHAM, TAC mice had higher TA velocity, LVP and LV weight and lower ejection fraction (EF) at three or nine weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared to compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening and more fibrosis. Both EF and LV mass measured by echo at three weeks post-TAC were predictive of the presence of HF at three or nine weeks post-TAC. Conclusions In wild type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echo three weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Variable phenotype in murine transverse aortic constriction

Mohammed

Storlie

Oehler

et al. 2012

Cardiovascular Pathology

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“…26 Celecoxib also significantly reduced insulin-induced Akt signalling and markers for cardiac hypertrophy in a rabbit myocyte model, as well as LV dilation, contractile dysfunction and mortality at 8 weeks in a mouse aortic banding model of heart failure. 27 Akt activation is believed to play an important role in maladaptive cardiac hypertrophy associated with heart failure. 28 Thus, COX-independent inhibition of Akt activation may explain, in part, the inhibition by celecoxib of the cardiac remodelling effects of aldosterone.…”

Section: Discussionmentioning

confidence: 99%

Celecoxib, but not rofecoxib or naproxen, attenuates cardiac hypertrophy and fibrosis induced in vitro by angiotensin and aldosterone

Wang

Bertucci²,

Yang

et al. 2010

Clin Exp Pharma Physio

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1. Cyclo-oxygenase (COX)-2 inhibitors and other non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in increased cardiovascular events. However, the direct effects of these drugs on cardiac function have not been explored extensively. Given the important role of the renin-angiotensin-aldosterone system (RAAS) in cardiac remodelling, we sought to determine the effect of COX-2 inhibitors and non-specific (NS-) NSAIDs on RAAS-induced cardiac hypertrophy and fibrosis in neonatal rat cardiac myocytes (NCM) and fibroblasts (NCF) isolated from 1-2-day-old Sprague-Dawley rat pups. 2. The NCM were pretreated for 2 h with COX-2 inhibitors (celecoxib or rofecoxib) or NS-NSAIDs (naproxen; all at 0.1-10 micromol/L) before being stimulated with 10 micromol/L aldosterone for 72 h or with 0.1 micromol/L angiotensin (Ang) II for 60 h. Hypertrophy of NCM was assessed by [3H]-leucine incorporation. 3. The NCF were pretreated with COX-2 inhibitors or naproxen as described for NCM before being stimulated with 0.1 micromol/L AngII for 48 h. Collagen synthesis was subsequently assayed by [3H]-proline incorporation. 4. Pooled cryopreserved male and female rat hepatocytes were treated with or without COX-2 inhibitors for 1 h before 1 nmol/L aldosterone ( approximately 540 pg/mL) was added to all wells. Cells were incubated for a further 60 min and culture media harvested by centrifugation. Human hepatic HepG2 cells were treated with compounds with or without serum starvation for 48 h. All cells were pretreated with COX-2 inhibitors for 2 h before the addition of aldosterone. Cell culture media were harvested after a further 3, 18, 24 or 48 h incubation. Aldosterone concentrations in the culture media were determined by enzyme immunoassay. 5. Aldosterone- and AngII-stimulated NCM hypertrophy was inhibited by celecoxib, but not by rofecoxib or naproxen. In NCF, AngII-stimulated collagen synthesis was inhibited by celecoxib and, to a lesser extent, by rofecoxib, whereas naproxen had no effect. The COX-2 inhibitors inhibited aldosterone uptake and/or metabolism by rat hepatocytes, but had no effect in human hepatic HepG2 cells. 6. These results demonstrate a potential antiremodelling effect of selective COX-2 inhibitors in the setting of RAAS stimulation in cardiac cells, whereas naproxen has no effect.

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“…TAC was performed as minimally invasive MTAB (minimally invasive transverse aortic banding) as described previously. 30 Cardiectomy was performed 1 day after echocardiography. Time from cardiectomy to freezing the samples in liquid nitrogen was less than 30 s. Left ventricles were isolated, ground in liquid nitrogen and shipped on dry ice.…”

Section: Methodsmentioning

confidence: 99%

High Precision Quantitative Proteomics Using iTRAQ on an LTQ Orbitrap: A New Mass Spectrometric Method Combining the Benefits of All

et al. 2009

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The development of quantitative techniques in mass spectrometry has generated the ability to systematically monitor protein expression. Isobaric tags for relative and absolute quantification (iTRAQ) have become a widely used tool for the quantification of proteins. However, application of iTRAQ methodology using ion traps and hybrid mass spectrometers containing an ion trap such as the LTQOrbitrap was not possible until the development of pulsed Q dissociation (PQD) and higher energy C-trap dissociation (HCD). Both methods allow iTRAQ-based quantification on an LTQ-Orbitrap but are less suited for protein identification at a proteomic scale than the commonly used collisional induced dissociation (CID) fragmentation. We developed an analytical strategy combining the advantages of CID and HCD, allowing sensitive and accurate protein identification and quantitation at the same time. In a direct comparison, the novel method outperformed PQD and HCD regarding its limit of detection, the number of identified peptides and the analytical precision of quantitation. The new method was applied to study changes in protein expression in mouse hearts upon transverse aortic constriction, a model for cardiac stress.

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Celecoxib modulates hypertrophic signalling and prevents load‐induced cardiac dysfunction

Cited by 20 publications

References 53 publications

Variable phenotype in murine transverse aortic constriction

Variable phenotype in murine transverse aortic constriction

Celecoxib, but not rofecoxib or naproxen, attenuates cardiac hypertrophy and fibrosis induced in vitro by angiotensin and aldosterone

High Precision Quantitative Proteomics Using iTRAQ on an LTQ Orbitrap: A New Mass Spectrometric Method Combining the Benefits of All

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