Exercise training prevents ventricular tachycardia in CPVT1 due to reduced CaMKII-dependent arrhythmogenic Ca2+ release.

Abstract:

AIMS:Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is caused by mutations in the cardiac ryanodine receptor (RyR2) that lead to disrupted Ca(2+) handling in cardiomyocytes and ventricular tachycardia. The aim of this study was to test whether exercise training could reduce the propensity for arrhythmias in mice with the CPVT1-causative missense mutation Ryr2-R2474S by restoring normal Ca(2+) handling. METHODS AND RESULTS:Ryr2-R2474S mice (RyR-RS) performed a 2 week interval treadmill exercise training protocol. Each exercise session comprised five 8 min intervals at 80-90% of the running speed at maximal oxygen uptake (VO2max) and 2 min active rest periods at 60%. VO2max increased by 10 ± 2% in exercise trained RyR-RS (ET), while no changes were found in sedentary controls (SED). RyR-RS ET showed fewer episodes of ventricular tachycardia compared with RyR-RS SED, coinciding with fewer Ca(2+) sparks and waves, less diastolic Ca(2+) leak from the sarcoplasmic reticulum, and lower phosphorylation levels at RyR2 sites associated with Ca(2) (+)-calmodulin-dependent kinase type II (CaMKII) compared with RyR-RS SED. The CaMKII inhibitor autocamtide-2-related inhibitory peptide and also the antioxidant N-acetyl-l-cysteine reduced Ca(2+) wave frequency in RyR-RS equally to exercise training. Protein analysis as well as functional data indicated a mechanism depending on reduced levels of oxidized CaMKII after exercise training. Two weeks of detraining reversed the beneficial effects of the interval treadmill exercise training protocol in RyR-RS ET. CONCLUSION:Long-term effects of interval treadmill exercise training reduce ventricular tachycardia episodes in mice with a CPVT1-causative Ryr2 mutation through lower CaMKII-dependent phosphorylation of RyR2.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Manotheepan R,Danielsen TK,Sadredini M,Anderson ME,Carlson CR,Lehnart SE,Sjaastad I,Stokke MK

doi

10.1093/cvr/cvw095

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

295-306

issue

3

eissn

0008-6363

issn

1755-3245

pii

cvw095

journal_volume

111

pub_type

杂志文章
  • m-Calpain antagonizes RhoA overactivation and endothelial barrier dysfunction under disturbed shear conditions.

    abstract:AIMS:It has been reported that laminar shear flow (LF) improves barrier functions in vascular endothelial cells (ECs), whereas disturbed flow (DF) impairs the barrier. Our previous study showed that LF stimulus led to the activation of the cysteine protease, m-calpain, in ECs, which can influence RhoA activity. We hypo...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp311

    authors: Miyazaki T,Honda K,Ohata H

    更新日期:2010-02-01 00:00:00

  • Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-kappaB/IkappaB- and ERK2-dependent mechanisms.

    abstract:OBJECTIVE:Oxidized low-density lipoproteins (ox-LDL) or their components suppress macrophage inflammatory response by down-regulating cytokine synthesis, nitric oxide synthase and inducible cyclooxygenase (Cox-2). This event is crucial for the pathophysiological process leading to the formation of atherosclerotic plaqu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00437-6

    authors: Eligini S,Brambilla M,Banfi C,Camera M,Sironi L,Barbieri SS,Auwerx J,Tremoli E,Colli S

    更新日期:2002-08-01 00:00:00

  • Tumor necrosis factor alpha as an endogenous stimulator for circulating coupling factor 6.

    abstract:OBJECTIVE:We recently showed that mitochondrial coupling factor 6 (CF6) is present as a pressor substance and a prostacyclin inhibitor in systemic circulation. However, the regulation mechanism for circulating CF6 is unknown. We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the generation and rele...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2004.01.031

    authors: Sasaki S,Osanai T,Tomita H,Matsunaga T,Magota K,Okumura K

    更新日期:2004-06-01 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

  • Effect of mechanical boundary conditions on orientation of angiogenic microvessels.

    abstract:AIM:Mechanical forces are important regulators of cell and tissue phenotype. We hypothesized that mechanical loading and boundary conditions would influence neovessel activity during angiogenesis. METHODS AND RESULTS:Using an in vitro model of angiogenesis sprouting and a mechanical loading system, we evaluated the ef...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvn055

    authors: Krishnan L,Underwood CJ,Maas S,Ellis BJ,Kode TC,Hoying JB,Weiss JA

    更新日期:2008-05-01 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

  • Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9.

    abstract:AIMS:Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed. The innate immune system, i.e. toll-like receptor (TLR) 2 and 4, significantly contributes to cardiac dysfunction. Little is known regarding TLR9 and its pathogenic ligand bacterial DNA in the myocardium. W...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvn011

    authors: Knuefermann P,Schwederski M,Velten M,Krings P,Ehrentraut H,Rüdiger M,Boehm O,Fink K,Dreiner U,Grohé C,Hoeft A,Baumgarten G,Koch A,Zacharowski K,Meyer R

    更新日期:2008-04-01 00:00:00

  • Effect of increases in afterload before and after coronary occlusion in awake dogs.

    abstract::Ventricular function curves relating stroke work and left ventricular end-diastolic pressure were generated in awake dogs during increases in preload produced by infusion of fluid and during increases in afterload produced by administration of phenylephrine. The ventricular function curves produced by preloading were ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/13.7.392

    authors: Rosenfeldt FL,Cobb FR,Bache RJ,Sabiston DC Jr

    更新日期:1979-07-01 00:00:00

  • Genetically modified mice: tools to decode the functions of connexins in the heart-new models for cardiovascular research.

    abstract::It has long been known that gap junctions are required for the propagation of electrical impulse in the heart. A good deal later, the connexins (Cxs), which are probably exclusive components of the junctional channels that constitute the gap junctions, were identified. More recently, the in vivo functions of cardiac C...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2004.02.010

    authors: Gros D,Dupays L,Alcoléa S,Meysen S,Miquerol L,Théveniau-Ruissy M

    更新日期:2004-05-01 00:00:00

  • Human Influenza A virus causes myocardial and cardiac-specific conduction system infection associated with early inflammation and premature death.

    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

    authors: Filgueiras-Rama D,Vasilijevic J,Jalife J,Noujaim SF,Alfonso JM,Nicolas-Avila JA,Gutierrez C,Zamarreño N,Hidalgo A,Bernabé A,Cop CP,Ponce-Balbuena D,Guerrero-Serna G,Calle D,Desco M,Ruiz-Cabello J,Nieto A,Falcon A

    更新日期:2020-04-28 00:00:00

  • Platelet-activating factor (PAF) does not affect diastolic function in isolated rat hearts.

    abstract::Platelet-activating factor might be responsible for the alterations of diastolic function observed in different disease states and these potential effects have not been studied. The effect of incremental concentrations of platelet-activating factor (to a maximum of 200 nM) was therefore examined in isolated perfused r...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(95)00181-6

    authors: Muñoz HR,Evans RD,Marsch SC,Foëx P

    更新日期:1995-12-01 00:00:00

  • Gene transfer and vascular disease.

    abstract::Major advances in molecular biology over the past decade have increased our understanding of how genes are expressed and regulated in mammalian cells in vivo. This knowledge has been translated to investigations of the molecular and cellular biology of the cardiovascular system. Gene transfer, the introduction of a re...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/28.4.445

    authors: Nabel EG,Pompili VJ,Plautz GE,Nabel GJ

    更新日期:1994-04-01 00:00:00

  • Cardiomyopathies in disorders of oxidative metabolism.

    abstract::Primary cardiomyopathy is an important cause of mortality in children and adults. Apart from inherited disorders of myocardial contractile and structural proteins, several defects of energy metabolism may cause cardiomyopathy. Most of the energy required for myocardial contraction is derived from aerobic metabolism. F...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(97)00141-7

    authors: Antozzi C,Zeviani M

    更新日期:1997-08-01 00:00:00

  • Indomethacin, but not oxygen tension, affects the sensitivity of isolated neonatal rabbit ductus arteriosus, but not aorta, to noradrenaline.

    abstract::The effects of increasing oxygen tension from fetal to neonatal levels and of incubation in the cyclo-oxygenase inhibitor, indomethacin, on the response of isolated rings of neonatal rabbit ductus arteriosus and aorta to noradrenaline were studied in vitro. Increasing oxygen tension did not affect the sensitivity, as ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/22.12.910

    authors: Smith GC,McGrath JC

    更新日期:1988-12-01 00:00:00

  • Transmural coronary vasodilator reserve, and flow distribution during tachycardia in conscious young swine with right ventricular hypertrophy.

    abstract::Regional distribution of myocardial blood flow (MBF) was examined in eight normal and nine pulmonary artery banded (PAB) pigs before and during pacing induced tachycardia (heart rates: 175, 225 and 275 beats X min-1) as well as during iv adenosine infusion (1.5 mg X kg-1 X min-1; maximal coronary vasodilatation) using...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/19.2.104

    authors: Manohar M

    更新日期:1985-02-01 00:00:00

  • Influence of experimental diabetes on the mechanical responses of canine coronary arteries: role of endothelium.

    abstract::The influence of experimental diabetes on the endothelium mediated relaxation and contractile responses of canine isolated coronary arteries was studied in arteries removed from alloxan treated diabetic (280 mmol.kg-1) and control mongrel dogs. Strips with and without endothelium were suspended in Krebs bicarbonate so...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/22.8.537

    authors: Gebremedhin D,Koltai MZ,Pogátsa G,Magyar K,Hadházy P

    更新日期:1988-08-01 00:00:00

  • Early exercise training after myocardial infarction prevents contractile but not electrical remodelling or hypertrophy.

    abstract:AIMS:Exercise started early after myocardial infarction (MI) improves in vivo cardiac function and myofilament responsiveness to Ca(2+). We investigated whether this represents partial or complete reversal of cellular remodelling. METHODS AND RESULTS:Mice with MI following left coronary ligation were given free access...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp381

    authors: Bito V,de Waard MC,Biesmans L,Lenaerts I,Ozdemir S,van Deel E,Abdel-Mottaleb Y,Driesen R,Holemans P,Duncker DJ,Sipido KR

    更新日期:2010-04-01 00:00:00

  • Effects of intracellular sodium and hydrogen ion on the sodium activated potassium channel in isolated patches from guinea pig ventricular myocytes.

    abstract:OBJECTIVE:The Na+ activated K+ channel (IK(Na)) may be activated during ischaemia when the intracellular Na+ concentration is raised. As ischaemia is also associated with intracellular acidification, the influence of intracellular pH on this K+ channel was investigated. METHODS:The effects of intracellular Na+ and H+ ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/28.7.1036

    authors: Veldkamp MW,Vereecke J,Carmeliet E

    更新日期:1994-07-01 00:00:00

  • Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis without increased bleeding risk.

    abstract:AIMS:Atrial fibrillation (AF) is a major risk factor for cardio-embolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern. This study sought to identify new targets to develop safer antithrombotic therapie...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvw049

    authors: Allende M,Molina E,Guruceaga E,Tamayo I,González-Porras JR,Gonzalez-López TJ,Toledo E,Rabal O,Ugarte A,Roldán V,Rivera J,Oyarzabal J,Montes R,Hermida J

    更新日期:2016-06-01 00:00:00

  • Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes.

    abstract:AIMS:To describe the overall role of reduced sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) for Ca(2+) wave development. METHODS AND RESULTS:SERCA2 knockout [Serca2(flox/flox) Tg(alphaMHC-MerCreMer); KO] mice allowing inducible cardiomyocyte-specific disruption of the Serca2 gene in adult mice were compared with Serca(...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp401

    authors: Stokke MK,Hougen K,Sjaastad I,Louch WE,Briston SJ,Enger UH,Andersson KB,Christensen G,Eisner DA,Sejersted OM,Trafford AW

    更新日期:2010-04-01 00:00:00

  • Separation of the oscillatory current from other currents in cardiac Purkinje fibres.

    abstract::An oscillatory current (Ios) can be recorded after depolarising clamps of a given amplitude and duration. To determine whether Ios depends on other currents activated during the clamp, the Ios was investigated in the absence and in the presence of 4-aminopyridine (4-AP) and cesium (Cs). The following results were obta...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/16.11.637

    authors: Mugelli A

    更新日期:1982-11-01 00:00:00

  • Mechanisms of the pro- and anti-oxidant actions of nitric oxide in atherosclerosis.

    abstract::The association of nitric oxide (NO) with cardiovascular disease has long been recognized and the extensive research on this topic has revealed both pro- and anti-atherosclerotic effects. While these contradictory findings were initially perplexing recent studies offer molecular mechanisms for the integration of these...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(00)00086-9

    authors: Patel RP,Levonen A,Crawford JH,Darley-Usmar VM

    更新日期:2000-08-18 00:00:00

  • Mouse electrocardiography: an interval of thirty years.

    abstract::The interest in mouse electrophysiology is expanding fast, despite the marked differences between mouse and man. Different methods have become available to analyse the electrical activity in the mouse heart in vivo. The mouse genome can be altered with relative ease, which allows the molecular dissection of the variou...

    journal_title:Cardiovascular research

    pub_type: 评论,杂志文章,评审

    doi:10.1016/s0008-6363(99)00335-1

    authors: Wehrens XH,Kirchhoff S,Doevendans PA

    更新日期:2000-01-01 00:00:00

  • Rho-kinase-mediated pathway induces enhanced myosin light chain phosphorylations in a swine model of coronary artery spasm.

    abstract:OBJECTIVE:We recently demonstrated in our swine model of coronary artery spasm that enhanced myosin light chain (MLC) phosphorylations (both MLC mono- and diphosphorylations) play a central role in the pathogenesis of the spasm. However, the molecular mechanism for and the phosphorylation sites for the enhanced MLC pho...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(99)00144-3

    authors: Shimokawa H,Seto M,Katsumata N,Amano M,Kozai T,Yamawaki T,Kuwata K,Kandabashi T,Egashira K,Ikegaki I,Asano T,Kaibuchi K,Takeshita A

    更新日期:1999-09-01 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

  • Binding of [3H]-5-hydroxytryptamine to human coronary artery and bypass graft vessels.

    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

    authors: Dahm PL,Bodelsson M,Törnebrandt K,Muddle JR,Sykes RM,Yacoub M,Dashwood MR

    更新日期:1996-05-01 00:00:00

  • Brain tumour necrosis factor-alpha modulates neurotransmitters in hypothalamic paraventricular nucleus in heart failure.

    abstract:AIMS:Increased proinflammatory cytokines after myocardial infarction augment the progression of heart failure (HF) and are of prognostic significance. Recently, we demonstrated that increased proinflammatory cytokines in the brains of HF rats increased paraventricular nucleus (PVN) superoxide and down-regulated neurona...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp160

    authors: Kang YM,He RL,Yang LM,Qin DN,Guggilam A,Elks C,Yan N,Guo Z,Francis J

    更新日期:2009-09-01 00:00:00

  • Nuclear accumulation of androgen receptor in gender difference of dilated cardiomyopathy due to lamin A/C mutations.

    abstract:AIMS:Dilated cardiomyopathy (DCM) is characterized by ventricular dilation associated with systolic dysfunction, which could be caused by mutations in lamina/C gene (LMNA). LMNA-linked DCM is severe in males in both human patients and a knock-in mouse model carrying a homozygous p.H222P mutation (LmnaH222P/H222P). The ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvt106

    authors: Arimura T,Onoue K,Takahashi-Tanaka Y,Ishikawa T,Kuwahara M,Setou M,Shigenobu S,Yamaguchi K,Bertrand AT,Machida N,Takayama K,Fukusato M,Tanaka R,Somekawa S,Nakano T,Yamane Y,Kuba K,Imai Y,Saito Y,Bonne G,Kimura A

    更新日期:2013-08-01 00:00:00

  • Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia.

    abstract:OBJECTIVES:Myocardial ischemia results in an early phase of arrhythmias that primarily involves reentrant mechanisms. However, the trigger that initiates reentry remains unknown. We studied the initiation of reentry attending the development of electrical heterogeneity during simulated ischemia in isolated canine right...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Lukas A,Antzelevitch C

    更新日期:1996-09-01 00:00:00

  • Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice.

    abstract:AIMS:Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investi...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp043

    authors: Liu SL,Li YH,Shi GY,Tang SH,Jiang SJ,Huang CW,Liu PY,Hong JS,Wu HL

    更新日期:2009-04-01 00:00:00