Calcineurin regulates NFAT-dependent iNOS expression and protection of cardiomyocytes: co-operation with Src tyrosine kinase.

Abstract:

OBJECTIVE:To determine the role of calcineurin and Src tyrosine kinase in the regulation of inducible nitric oxide synthase (iNOS) expression and protection in cardiomyocytes. METHODS:iNOS expression was studied in isolated neonatal rat ventricular myocyte cultures in response to bacterial lipopolysaccharide (LPS) or following transfection with constitutively active calcineurin or Src and in hearts isolated from wild-type or calcineruin Abeta knockout mice. Cell injury in response to simulated ischemia-reperfusion was studied following overexpression of active calcineurin. Regulation of the iNOS gene promoter by calcineurin was studied using promoter-luciferase reporter and chromatin immunoprecipitation assays. RESULTS:Overexpression of constitutively active Src co-operated with [Ca2+]c elevation to induce iNOS expression, and LPS-induced iNOS expression was abrogated by pharmacological inhibition of calcineurin or tyrosine kinase. LPS also induced tyrosine kinase-dependent but calcineurin-independent phosphorylation of Src Tyr418. LPS induced myocardial iNOS expression in wild-type but not calcineurin Abeta knockout mice. Overexpression of constitutively active calcinuerin in isolated cardiomyocytes caused dephosphorylation and nuclear accumulation of the c1 isoform of nuclear factor of activated T-cells (NFATc1), induced strong iNOS expression, and induced NOS-dependent protection against simulated ischemia-reperfusion prior to cardiomyocyte hypertrophy. Co-transfection of a mouse iNOS promoter-luciferase reporter in combination with active calcineurin and wild-type or dominant negative Src confirmed that constitutive activation of calcineurin was sufficient for transactivation. Chromatin immunoprecipitation confirmed calcineurin-dependent in vivo binding of NFATc1 to consensus sites within the iNOS promoter. CONCLUSIONS:These results support a cardioprotective role for calcineurin mediated by NFAT-dependent induction of iNOS expression and co-operativity between calcineurin and Src.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Obasanjo-Blackshire K,Mesquita R,Jabr RI,Molkentin JD,Hart SL,Marber MS,Xia Y,Heads RJ

doi

10.1016/j.cardiores.2006.05.026

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

672-83

issue

4

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(06)00251-3

journal_volume

71

pub_type

杂志文章
  • Hypoxia induces unique proliferative response in adventitial fibroblasts by activating PDGFβ receptor-JNK1 signalling.

    abstract:AIMS:Pulmonary hypertension (PH) is a devastating condition for which no disease-modifying therapies exist. PH is recognized as proliferative disease of the pulmonary artery (PA). In the experimental newborn calf model of hypoxia-induced PH, adventitial fibroblasts in the PA wall exhibit a heightened replication index....

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvs194

    authors: Panzhinskiy E,Zawada WM,Stenmark KR,Das M

    更新日期:2012-08-01 00:00:00

  • Orphan targets for reperfusion injury.

    abstract::Cardiomyocyte death secondary to transient ischaemia occurs mainly during the first minutes of reperfusion in the form of contraction band necrosis. Research on the mechanisms leading to sarcolemmal rupture and necrosis during initial reperfusion identified several promising pharmacological targets directed either to ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvp109

    authors: Inserte J,Barrabés JA,Hernando V,Garcia-Dorado D

    更新日期:2009-07-15 00:00:00

  • Role of glycolytic flux in effect of glucose in decreasing fatty-acid-induced release of lactate dehydrogenase from isolated coronary ligated rat heart.

    abstract::The mechanisms whereby glucose reduces fatty acid-induced release of enzyme from the coronary-ligated isolated perfused working rat heart are investigated. Alterations in the tissue contents of ATP, phosphocreatine, or glycogen could be excluded as possible mechanisms for the beneficial effect of glucose in this syst...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/13.12.693

    authors: Opie LH,Bricknell OL

    更新日期:1979-12-01 00:00:00

  • Animal models of human cardiovascular disease, heart failure and hypertrophy.

    abstract::The progress made in our understanding of the pathophysiology and treatment of congestive heart failure (CHF) would not have been possible without a number of animal models of heart failure and hypertrophy, each one having unique advantages as well as disadvantages. The species and interventions used to create CHF dep...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(98)00110-2

    authors: Hasenfuss G

    更新日期:1998-07-01 00:00:00

  • Aerobic interval training attenuates remodelling and mitochondrial dysfunction in the post-infarction failing rat heart.

    abstract:AIMS:Following a large myocardial infarction (MI), remaining viable muscle often undergoes pathological remodelling and progresses towards chronic heart failure. Mitochondria may also be affected by this process and, due to their functional importance, likely contribute to the progression of the disease. Aerobic interv...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvt080

    authors: Kraljevic J,Marinovic J,Pravdic D,Zubin P,Dujic Z,Wisloff U,Ljubkovic M

    更新日期:2013-07-01 00:00:00

  • Mitochondrial K(ATP) channels: role in cardioprotection.

    abstract::The role of the mitochondrial ATP-sensitive potassium channel (mK(ATP)) in ischemic preconditioning and cardioprotection is reviewed. A great deal of accumulated evidence implicatese opening of this channel as an important step in the anti-infarct effect of ischemic preconditioning. Recent studies, however, reveal tha...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(02)00439-x

    authors: Oldenburg O,Cohen MV,Yellon DM,Downey JM

    更新日期:2002-08-15 00:00:00

  • Deaminovasopressin has direct and modulatory effects on ventricular automaticity in the rat heart.

    abstract:OBJECTIVE:Some neuropeptides have direct cardiac effects and also modulate the cardiac effects of catecholamines. Vasopressin is an abundantly available neuropeptide having well known interactions with catecholamines in vascular smooth muscle. The aim of this study was to determine the direct and modulatory effects of ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.9.1624

    authors: Sun LS,Sawyer WH,Steinberg SF,Rosen MR

    更新日期:1993-09-01 00:00:00

  • Endothelin B receptor-mediated vasoconstriction induced by endothelin A receptor antagonist.

    abstract:OBJECTIVE:The vasoconstrictor effect of endothelins (ET) is mediated by endothelin A (ETA) and endothelin B (ETB) receptors. Furthermore, ETB receptor stimulation results in release of vasodilators. Hence, ETA receptor antagonists should attenuate ET-mediated vasoconstriction. The aim of the present study was to evalua...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(98)00152-7

    authors: Zhang Y,Oliver JR,Horowitz JD

    更新日期:1998-09-01 00:00:00

  • ATP antagonism of thrombin-induced endothelial barrier permeability.

    abstract:OBJECTIVES:Thrombin induces endothelial barrier failure by activating the contractile machinery of endothelial cells. Contractile activation is due to an increase in myosin light chain (MLC) phosphorylation. Here, it was investigated whether stimulation of endothelial cells with ATP can interrupt this thrombin-induced ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(03)00427-9

    authors: Gündüz D,Hirche F,Härtel FV,Rodewald CW,Schäfer M,Pfitzer G,Piper HM,Noll T

    更新日期:2003-08-01 00:00:00

  • Effect of pressure overload on cardiac Ca2+ antagonist binding sites of guinea pig. Comparison with the adaptational response of the hypertrophied rat heart.

    abstract:STUDY OBJECTIVE:The aim was to determine if the adaptational process of the cardiac calcium channel to pressure overload observed in rat heart also occurs in species characterised by a higher sensitivity to external calcium than in the rat. This adaptation occurs via a maintained density of dihydropyridine receptors an...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/25.10.875

    authors: Primot I,Mayoux E,Oliviero P,Charlemagne D

    更新日期:1991-10-01 00:00:00

  • L-Arginine inhibits neutrophil adherence and coronary artery dysfunction.

    abstract:BACKGROUND:Nitric oxide (NO) attenuates neutrophil (PMN)-mediated damage, partly by inhibiting superoxide anion (O2-) generation and adherence to the coronary artery endothelium. L-Arginine is the endogenous substrate for production of NO via the NO synthase pathway. This study tested the hypothesis that the endogenous...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Sato H,Zhao ZQ,Vinten-Johansen J

    更新日期:1996-01-01 00:00:00

  • Superoxide dismutase and N-2-mercaptopropionyl glycine attenuate infarct size limitation effect of ischaemic preconditioning in the rabbit.

    abstract:OBJECTIVE:Ischaemic preconditioning may be mediated by oxygen free radicals generated during preconditioning. Conflicting results have been reported regarding the effect of superoxide dismutase (SOD) in attenuating the cardioprotective effect of preconditioning. The aim of the study was to reconcile this conflict by ex...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/28.7.980

    authors: Tanaka M,Fujiwara H,Yamasaki K,Sasayama S

    更新日期:1994-07-01 00:00:00

  • Transgenic alpha1A-adrenergic activation limits post-infarct ventricular remodeling and dysfunction and improves survival.

    abstract:OBJECTIVE:Myocardial contractility is enhanced in transgenic (TG) mice with cardiac-restricted overexpression of the alpha1A-adrenergic receptors (alpha1A-AR). We tested the hypothesis that this enhanced inotropy protects against dysfunction and remodeling after myocardial infarction (MI). METHODS:We subjected alpha1A...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2006.06.015

    authors: Du XJ,Gao XM,Kiriazis H,Moore XL,Ming Z,Su Y,Finch AM,Hannan RA,Dart AM,Graham RM

    更新日期:2006-09-01 00:00:00

  • Endothelium independent relaxation of human coronary arteries by 17 beta-oestradiol in vitro.

    abstract:OBJECTIVE:There is accumulating evidence that oestrogen replacement therapy protects against the development of coronary atherosclerosis and myocardial infarction in postmenopausal women. The mechanism of this protective effect is uncertain. The aim of this study was to measure the effects of 17 beta-oestradiol on huma...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.11.1939

    authors: Mügge A,Riedel M,Barton M,Kuhn M,Lichtlen PR

    更新日期:1993-11-01 00:00:00

  • Peroxisome proliferation-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis.

    abstract:BACKGROUND:Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands have been shown to ameliorate a variety of inflammatory conditions. The present study tested the hypothesis that PPAR-gamma ligands reduce experimental autoimmune myocarditis (EAM) associated with inhibition of the expansion and activation...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(03)00457-7

    authors: Yuan Z,Liu Y,Liu Y,Zhang J,Kishimoto C,Wang Y,Ma A,Liu Z

    更新日期:2003-09-01 00:00:00

  • Cbx3 inhibits vascular smooth muscle cell proliferation, migration, and neointima formation.

    abstract:Aims:To investigate the role of chromobox protein homolog 3 (Cbx3) in vascular smooth muscle cell (VSMC) proliferation, migration, and neointima formation following vascular injury. Methods and results:Overexpression of Cbx3 led to a significant increase in VSMC contractile gene expression and VSMC apoptosis as well a...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvx236

    authors: Zhang C,Chen D,Maguire EM,He S,Chen J,An W,Yang M,Afzal TA,Luong LA,Zhang L,Lei H,Wu Q,Xiao Q

    更新日期:2018-03-01 00:00:00

  • Liposomal Hsp90 cDNA induces neovascularization via nitric oxide in chronic ischemia.

    abstract:OBJECTIVE:Induction of angiogenesis has been reported subsequent to eNOS overexpression or activation, the latter involving Hsp90 as a chaperone protein. Here, we investigated the potential of regional Hsp90 overexpression to induce therapeutic neovascularization in vivo in a chronic rabbit hindlimb ischemia model. ME...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2004.10.019

    authors: Pfosser A,Thalgott M,Büttner K,Brouet A,Feron O,Boekstegers P,Kupatt C

    更新日期:2005-02-15 00:00:00

  • Reduced cardiac hypertrophy in toll-like receptor 4-deficient mice following pressure overload.

    abstract:OBJECTIVE:We have previously demonstrated that nuclear factor kappa B (NFkappaB) activation is needed for the development of cardiac hypertrophy in vivo. NFkappaB is a downstream transcription factor in the Toll-like receptor (TLR)-mediated signaling pathway; therefore, we investigated a role of TLR4 in cardiac hypertr...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2005.05.025

    authors: Ha T,Li Y,Hua F,Ma J,Gao X,Kelley J,Zhao A,Haddad GE,Williams DL,William Browder I,Kao RL,Li C

    更新日期:2005-11-01 00:00:00

  • Pathophysiological significance of coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion in anaesthetised dogs.

    abstract::The significance of pre-existing coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion was studied in anaesthetised open-chest dogs. The extent of myocardial ischaemic damage was assessed by the accumulation of calcium in the central zone of the ischaemic area and the size o...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/14.5.288

    authors: Tanabe M,Fujiwara S,Ohta N,Shimamoto N,Hirata M

    更新日期:1980-05-01 00:00:00

  • Stretch-induced modifications of myocardial performance: from ventricular function to cellular and molecular mechanisms.

    abstract::The purpose of this review is to give an integrative view of the effect of stretch on the myocardium from ventricular function changes to cellular and molecular mechanisms. The general approach will be to discuss the cellular and molecular events which can explain the findings obtained in the whole ventricle. Followin...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:

    authors: Crozatier B

    更新日期:1996-07-01 00:00:00

  • Metformin directly suppresses atherosclerosis in normoglycemic mice via haematopoietic Adenosine Monophosphate-Activated Protein Kinase (AMPK).

    abstract:AIMS:Atherosclerotic vascular disease has an inflammatory pathogenesis. Heme from intraplaque hemorrhage may drive a protective and pro-resolving macrophage M2-like phenotype, Mhem, via AMPK and ATF1. The anti-diabetic drug metformin may also activate AMPK-dependent signalling. HYPOTHESIS:Metformin systematically indu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvaa171

    authors: Seneviratne A,Cave L,Hyde G,Moestrup SK,Carling D,Mason JC,Haskard DO,Boyle JJ

    更新日期:2020-07-15 00:00:00

  • Evidence for the stimulatory effect of resveratrol on Ca(2+)-activated K+ current in vascular endothelial cells.

    abstract:OBJECTIVE:Resveratrol, a natural phytoalexin compound, is present in grapes and wine, and it can produce vasorelaxation. However, little is known of its mechanisms of action on ionic currents in endothelial cells. METHODS:The effect of resveratrol on Ca(2+)-activated K+ currents in an endothelial cell line (HUV-EC-C) ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(99)00397-1

    authors: Li HF,Chen SA,Wu SN

    更新日期:2000-03-01 00:00:00

  • End tidal carbon dioxide as an haemodynamic determinant of cardiopulmonary resuscitation in the rat.

    abstract::End tidal PCO2 (PETCO2) has been found to be a good prognostic indicator of successful resuscitation from cardiac arrest. To explore the value of this measurement further, we carried out a series of experiments during cardiac arrest and closed chest resuscitation in 14 mechanically ventilated Sprague-Dawley rats. Vent...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/23.4.364

    authors: von Planta M,von Planta I,Weil MH,Bruno S,Bisera J,Rackow EC

    更新日期:1989-04-01 00:00:00

  • Mechanosensitive nonselective cation channel facilitation by endothelin-1 is regulated by protein kinase C in arterial myocytes.

    abstract:OBJECTIVE:The mechanosensitive nonselective cation channel (NSC(MS)) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSC(MS) and on the myogenic response of arteries. METHODS:Cell-attached patch-clamp techniques were applied...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2007.06.021

    authors: Lee HA,Baek EB,Park KS,Jung HJ,Kim JI,Kim SJ,Earm YE

    更新日期:2007-11-01 00:00:00

  • An angiotensin II receptor antagonist attenuates left ventricular dilatation after myocardial infarction in the hypertensive rat.

    abstract:OBJECTIVE:The aims were (1) to investigate the effect of hypertention on left ventricular dilatation and haemodynamic alterations following acute myocardial infarction in spontaneously hypertensive rats (SHR) and normotensive rats (WKY); (2) to compare haemodynamic indices between the two groups; (3) to assess whether ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Nishikimi T,Yamagishi H,Takeuchi K,Takeda T

    更新日期:1995-06-01 00:00:00

  • Altered response to ibutilide in a heart failure model.

    abstract:OBJECTIVE:Despite the frequent use of anti-arrhythmic drugs in the general population, the electrophysiologic effects of these agents have not been elucidated in congestive heart failure (CHF). METHODS:To examine the impact of left ventricular dysfunction on actions of type III anti-arrhythmic drugs, we evaluated the ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00235-2

    authors: Chugh SS,Johnson SB,Packer DL

    更新日期:2001-01-01 00:00:00

  • The contribution of sleep to social inequalities in cardiovascular disorders: a multi-cohort study.

    abstract:AIMS:Sleep disturbances exhibit a strong social patterning, and inadequate sleep has been associated with adverse health outcomes, including cardiovascular disorders (CVD). However, the contribution of sleep to socioeconomic inequalities in CVD is unclear. This study pools data from eight European cohorts to investigat...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvz267

    authors: Petrovic D,Haba-Rubio J,de Mestral Vargas C,Kelly-Irving M,Vineis P,Kivimäki M,Nyberg S,Gandini M,Bochud M,Vollenweider P,d'Errico A,Barros H,Fraga S,Goldberg M,Zins M,Steptoe A,Delpierre C,Heinzer R,Carmeli C,Chade

    更新日期:2020-07-01 00:00:00

  • Raised blood pressure, not renin-angiotensin systems, causes cardiac fibrosis in TGR m(Ren2)27 rats.

    abstract:OBJECTIVES:Elevated systemic arterial blood pressure is associated with left ventricular hypertrophy and fibrosis. It has been suggested that both circulating and local myocardial renin-angiotensin systems play a role in mediating these responses. Here we describe the natural history of ventricular hypertrophy and fibr...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00063-8

    authors: Bishop JE,Kiernan LA,Montgomery HE,Gohlke P,McEwan JR

    更新日期:2000-07-01 00:00:00

  • Comparative DNA methylation and gene expression analysis identifies novel genes for structural congenital heart diseases.

    abstract:AIMS:For the majority of congenital heart diseases (CHDs), the full complexity of the causative molecular network, which is driven by genetic, epigenetic, and environmental factors, is yet to be elucidated. Epigenetic alterations are suggested to play a pivotal role in modulating the phenotypic expression of CHDs and t...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvw195

    authors: Grunert M,Dorn C,Cui H,Dunkel I,Schulz K,Schoenhals S,Sun W,Berger F,Chen W,Sperling SR

    更新日期:2016-10-01 00:00:00

  • NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid body chemoreceptor sensitivity in heart failure rabbits.

    abstract:OBJECTIVE:A previous study from this laboratory showed that elevation of endogenous angiotensin II (Ang II) and upregulation of the angiotensin II type 1 (AT(1)) receptor in the carotid body (CB) are involved in the enhanced peripheral chemoreceptor sensitivity in rabbits with chronic heart failure (CHF). NADPH oxidase...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2007.04.006

    authors: Li YL,Gao L,Zucker IH,Schultz HD

    更新日期:2007-08-01 00:00:00