Abstract:
AIMS:Both cyclooxygenase-2 (COX-2) and the transcription factor signal transducer and activator of transcription 3 (Stat3) are involved in adaptive growth and survival of cardiomyocytes. In ventricular cardiomyocytes, prostaglandin E(2) (PGE(2)), a major COX-2 product, leads to adaptive growth via Stat3 activation, but whether this transcription factor acts as a signalling molecule in PGE(2)-induced cell survival is unknown. Therefore, the purpose of this study was to determine whether PGE(2) counteracts cardiac apoptosis induced by doxorubicin (DOX), and if so, whether Stat3 plays a critical role in this cardioprotective effect. METHODS AND RESULTS:Neonatal rat ventricular cardiomyocytes were incubated with DOX (0.5 microM) and/or PGE(2) (1 microM). Apoptosis was assessed by determining caspase3 activation and apoptotic DNA fragmentation. The role of Stat3 was evaluated in vitro and in vivo by transfecting cardiomyocytes with siRNA targeting rat Stat3 and by using cardiomyocyte-restricted Stat3 knockout (Stat3 KO) mice, respectively. Incubation of ventricular cardiomyocytes with PGE(2) led to a time-dependent decrease in the DOX-induced caspase3 activation, reaching a maximal inhibition of 70 +/- 5% after 4 h. Similarly, PGE(2) inhibited DOX-induced DNA fragmentation by 58 +/- 5% after 24 h. This antiapoptotic action of PGE(2) was strongly reduced by the ERK1/2 inhibitor, U0126, whereas the p38 MAP kinase inhibitor, SB203580, had no effect. Depleting Stat3 expression by 50-60% in isolated ventricular cardiomyocytes markedly reduced the protective effect of PGE(2) on DOX-induced caspase3 activation and DNA fragmentation. Likewise, the stable PGE(2) analogue, 16,16-dimethyl-PGE(2), was unable to counteract cardiac apoptosis induced by DOX in Stat3 KO mice. CONCLUSION:Our results demonstrate that PGE(2) prevents myocardial apoptosis induced by DOX. This protection requires the activation of the prosurvival pathways of Stat3 and ERK1/2.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Frias MA,Somers S,Gerber-Wicht C,Opie LH,Lecour S,Lang Udoi
10.1093/cvr/cvn171subject
Has Abstractpub_date
2008-10-01 00:00:00pages
69-77issue
1eissn
0008-6363issn
1755-3245pii
cvn171journal_volume
80pub_type
杂志文章abstract:OBJECTIVE:We have previously shown that cardiac-directed expression of adenylycyclase type VI (AC(VI)) increases heart function in transgenic mice, and improves heart function and survival in murine cardiomyopathy. However, a potential problem of crossbreeding paradigms that use lines with two constitutively active tra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00539-4
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVES:To elucidate the effect of selective endothelin ET(A)- and mixed ET(A/B)-receptor antagonists on endothelial vasomotor dysfunction in rats with heart failure after myocardial infarction (MI). METHODS:Vasoreactivity and superoxide anion formation were determined in aortic rings from Wistar rats 12 weeks afte...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00083-3
更新日期:2000-07-01 00:00:00
abstract::Mouse models have been frequently used in the study of Chlamydia pneumoniae (also known as Chlamydophila pneumoniae) infections. This gram-negative obligate intracellular bacterium causes respiratory infections, followed by dissemination of the bacterium to various organs throughout the body, including cardiovascular ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.09.031
更新日期:2005-02-01 00:00:00
abstract:OBJECTIVE:Hemodynamic stresses are considered to be important regulators of gene expression in vascular cells. In this study, we have investigated the role of shear stress on ACE expression in cultured rat vascular cells, and focused on the regulation of ACE expression in smooth muscle cells. METHODS:Rat aortic endoth...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00269-2
更新日期:2000-01-14 00:00:00
abstract:OBJECTIVE:The role of phosphorylation of the ryanodine receptor at serine-2808 (RyRS2808) in congestive heart failure (CHF) is controversial, and effects of RyRS2808 phosphorylation on contraction are unclear. It has been reported that diastolic sarcomere length (SL) fluctuations accompany propagating contractile waves...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.07.010
更新日期:2006-01-01 00:00:00
abstract:STUDY OBJECTIVE:Protective effects of nipradilol, a newly synthesised vasodilating beta adrenoceptor antagonist, isosorbide dinitrate, and bunazosin on coronary artery constriction induced by intracoronary injection of acetylcholine were determined by coronary arteriography and compared in vivo in pigs. DESIGN:Acetylc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.12.1013
更新日期:1990-12-01 00:00:00
abstract:AIMS:Altered Ca(2+) handling in atrial fibrillation (AF) has been associated with dysregulated protein phosphatase 1 (PP1) and subcellular heterogeneities in protein phosphorylation, but the underlying mechanisms remain unclear. This is due to a lack of investigation into the local, rather than global, regulation of PP...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu123
更新日期:2014-07-01 00:00:00
abstract::In this study we report about the modulation of connexin45 (Cx45) gap junction channel properties by phosphorylation of the connexin molecules through different protein kinases. Phosphorylation of Cx45 was studied in HeLa cells transfected with mouse Cx45 (mCx45). Using Western blotting (WB) and immunocytochemistry, t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00047-x
更新日期:2000-06-01 00:00:00
abstract::Microelectrode recordings of skin nerve sympathetic activity were made in the median nerve supplying the right hand of nine patients with Raynaud's phenomenon and 10 control subjects. With subjects warmed up (finger temperature 33 to 34 degrees C) different manoeuvres were used to evoke strong, single sympathetic burs...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.5.249
更新日期:1985-05-01 00:00:00
abstract:OBJECTIVE:The aims of the study were to determine the effect of chronic pressure overload of the left ventricle on the density and distribution of neuropeptide-Y-like immunoreactive (NPY-LI) nerve fibres in heart and to compare any changes to those observed in adrenergic nerve fibres, identified by dopamine beta-hydrox...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.3.494
更新日期:1993-03-01 00:00:00
abstract:AIMS:Free fatty acids induce apoptosis in cardiomyocytes, which is implicated in lipotoxic cardiomyopathy. However, the underlying mechanisms remain not fully understood. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr145
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVES:Pericardial effusion has long been associated with low voltage of the surface electrocardiogram and its clinical utility is well known. The cause of this reduced QRS voltage has usually been attributed to short circuiting of the impulses by the pericardial fluid, but its precise mechanism has not been clearl...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.1033
更新日期:1993-06-01 00:00:00
abstract:AIMS:Caveolae are membrane microdomains where important signalling pathways are assembled and molecular effects transduced. In this study, we hypothesized that shear stress-mediated vasodilation (SSD) of mouse small coronary arteries (MCA) is caveolae-dependent. METHODS AND RESULTS:MCA (80-150 μm) isolated from wild-t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt157
更新日期:2013-10-01 00:00:00
abstract::The cardioprotective effects of mioflazine, a recently developed cardiovascular drug, were investigated in 41 anaesthetised open chest Beagle dogs subjected to 1 h normothermic global myocardial ischaemia. The severity of the model is evidenced by the finding that only one out of 20 control dogs could be weaned from e...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.9.528
更新日期:1984-09-01 00:00:00
abstract::The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.8.655
更新日期:1989-08-01 00:00:00
abstract:OBJECTIVES:Collagen synthesis is one of the major mechanisms of primary atherosclerotic plaque growth and is likely to be similarly important in restenosis. The patterns of collagen gene expression in human restenosis and associations with thrombosis/hemorrhage have not been described. METHODS:Using human coronary art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract:AIMS:Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capac...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa117
更新日期:2020-04-28 00:00:00
abstract:OBJECTIVE:Oxidized low-density lipoprotein (ox-LDL) increases superoxide anion (O(2)(-)) production by the endothelial nitric oxide (NO) synthase (eNOS). We assessed whether the uncoupling of eNOS was associated with alterations in eNOS phosphorylation and/or the assembly of the eNOS signaling complex. METHODS AND RES...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.11.003
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVES:5-Hydroxytryptamine (5-HT) has a wide range of vascular effects mediated via specific receptors and it has been suggested to be a mediator in ischemic heart disease. The aim of the present study was to localise the 5-HT receptors within the vessel wall. METHODS:Epicardial coronary arteries obtained from pat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00029-6
更新日期:1996-05-01 00:00:00
abstract:OBJECTIVE:The function of angiotensin converting enzyme (ACE) at cell sites of high collagen turnover, such as heart valves, is uncertain. The aim of this study was to assess ACE and kininase-II-like activities and collagen turnover in cultured valvular interstitial cells of the adult rat heart. METHODS:The valvular i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVE:Mechanoelectric Feedback, a mechanical intervention inducing an electrical change, is gaining credence as a cause of cardiac arrhythmia in the clinical situation. However, the precise mechanism is unknown. To elucidate this we investigated mechanical and chemical modulation of stretch-induced premature ventri...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00314-3
更新日期:1998-04-01 00:00:00
abstract:AIM:The interaction between TNF-like weak inducer of apoptosis (TWEAK, Tnfsf12) and the receptor, fibroblast growth factor-inducible 14 (Fn14), regulates vascular damage through different mechanisms, including inflammation. Oxidative stress plays a major role in inflammation and the development of atherosclerosis, but ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv204
更新日期:2015-10-01 00:00:00
abstract::This paper puts emphasis on pioneers who developed cardiac flow dynamics concepts during the second half of the 20th century at a period where pressure measurements were the rule. Thinking flow instead of pressure dynamics corresponded to in-depth conceptual changes: whereas blood pressure generally has a single posit...
journal_title:Cardiovascular research
pub_type: 社论,历史文章
doi:10.1016/s0008-6363(01)00307-8
更新日期:2001-08-01 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is the most common cardiac arrhythmia, and early-onset lone AF has been linked to mutations in genes encoding ion channels. Mutations in the pore forming subunit KV4.3 leading to an increase in the transient outward potassium current (Ito) have previously been associated with the Brugada S...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt028
更新日期:2013-06-01 00:00:00
abstract::If the posterior hypothalamus contributes to elevate blood pressure in hypertension by increasing sympathetic vasomotor activity, then lesions of the posterior hypothalamus should lower blood pressure more in hypertensive than in normotensive rats. To test this hypothesis without complications caused by anaesthesia, a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.6.663
更新日期:1976-11-01 00:00:00
abstract:OBJECTIVE:Air bubbles entering the coronary artery may have harmful effects on cardiac function. From the physical point of view it is the relatively high surface tension of the blood-air interface which causes bubbles to trap in small vessels. The aim of the present study was to reduce depression of myocardial functio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00063-1
更新日期:1997-06-01 00:00:00
abstract:OBJECTIVES:Epidemiological evidence in humans suggests that intrauterine growth retardation is associated with an increased risk of hypertension and coronary heart disease in later life. To begin to understand the mechanisms involved, we developed and exploited a rat model of intrauterine growth retardation to assess p...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00167-x
更新日期:2000-11-01 00:00:00
abstract::Mechanical stress signals transmitted through the heart walls during hemodynamic loading are sensed by the myocytes, which respond with changes in contractile performance and gene expression. External forces play an important role in physiological heart development and hypertrophy, but disruption of the well-balanced ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2007.03.029
更新日期:2008-03-01 00:00:00
abstract:OBJECTIVE:Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.09.015
更新日期:2006-01-01 00:00:00
abstract::To provide further evidence that the veratrum alkaloids' mechanical, positive inotropic effect and not their chemical depolarising action predominates in initiating the left ventricular mechanoreceptor (including the Bezold) reflex the effect of intracoronary KCl, a chemical depolarising agent like the veratrum alkalo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.8.514
更新日期:1984-08-01 00:00:00