Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine MI model.

Abstract:

RATIONALE:Yes-associated protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte proliferation. OBJECTIVE:We hypothesized that YAP activation after myocardial infarction (MI) would preserve cardiac function and improve survival. METHODS AND RESULTS:We used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after MI preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP (hYAP) in the adult murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated expression of cell cycle genes and promoted a less mature cardiac gene expression signature. CONCLUSIONS:Cardiac-specific YAP activation after MI mitigated myocardial injury, improved cardiac function, and enhanced survival. These findings suggest that therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI.

journal_name

Circ Res

journal_title

Circulation research

authors

Lin Z,von Gise A,Zhou P,Gu F,Ma Q,Jiang J,Yau AL,Buck JN,Gouin KA,van Gorp PR,Zhou B,Chen J,Seidman JG,Wang DZ,Pu WT

doi

10.1161/CIRCRESAHA.115.303632

subject

Has Abstract

pub_date

2014-07-18 00:00:00

pages

354-63

issue

3

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.115.303632

journal_volume

115

pub_type

杂志文章
  • Relative roles of cardiac and arterial baroreceptors in vasopressin regulation during hemorrhage in conscious dogs.

    abstract::To determine the relative roles of cardiac and sinoaortic baroreceptors in mediation of arginine vasopressin (AVP) release, hemorrhage was performed in five groups of conscious splenectomized dogs: 1) all nerves intact; 2) either chronic surgical or acute pharmacological (intrapericardial lidocaine) cardiac denervatio...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.5.1422

    authors: Shen YT,Cowley AW Jr,Vatner SF

    更新日期:1991-05-01 00:00:00

  • Identification of an angiotensin receptor in rabbit renomedullary interstitial cells in tissue culture. Correlation with prostaglandin biosynthesis.

    abstract::High affinity binding sites of angiotensin II (A II) have been characterized in rabbit renomedullary interstitial cells in tissue culture. Binding was rapid, specific, and saturable. Scatchard analysis of steady state saturation binding data at 22 degrees C indicated a single binding site with an equilibrium dissociat...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.46.6.802

    authors: Brown CA,Zusman RM,Haber E

    更新日期:1980-06-01 00:00:00

  • Ionic current basis of electrocardiographic waveforms: a model study.

    abstract::Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiograph...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.0000016960.61087.86

    authors: Gima K,Rudy Y

    更新日期:2002-05-03 00:00:00

  • Effects of cytosolic ATP on Ca(2+) sparks and SR Ca(2+) content in permeabilized cardiac myocytes.

    abstract::Confocal imaging was used to study the influence of cytosolic ATP on the properties of spontaneous Ca(2+) sparks in permeabilized ventricular myocytes. Cells were perfused with mock intracellular solutions containing fluo 3. Reducing [ATP] to <0.5 mmol/L decreased the frequency but increased the amplitude of spontaneo...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh1801.096264

    authors: Yang Z,Steele DS

    更新日期:2001-09-14 00:00:00

  • Increase in functional Ca2+ channels in cerebral smooth muscle with renal hypertension.

    abstract::The hypothesis that availability of functional Ca2+ channels in vascular smooth muscle is augmented in hypertension was tested in basilar artery cells from Wistar rats exhibiting stable systolic blood pressure (BPsys) for 2 to 11 weeks after partial renal artery ligation (Goldblatt 2-kidney 1-clip [2K1C] model). Cells...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.12.1330

    authors: Simard JM,Li X,Tewari K

    更新日期:1998-06-29 00:00:00

  • Novel pharmacophores of connexin43 based on the "RXP" series of Cx43-binding peptides.

    abstract::Gap junction pharmacology is a nascent field. Previous studies have identified molecules that enhance intercellular communication, and may offer potential for innovative antiarrhythmic therapy. However, their specific molecular target(s) and mechanism(s) of action remain unknown. Previously, we identified a 34-aa pept...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.200576

    authors: Verma V,Larsen BD,Coombs W,Lin X,Spagnol G,Sorgen PL,Taffet SM,Delmar M

    更新日期:2009-07-17 00:00:00

  • Hirudin and nitrates inhibit the thrombin-induced release of endothelin from the intact porcine aorta.

    abstract::In intact porcine aorta, endothelium-derived nitric oxide released on thrombin stimulation inhibits the concomitant production of endothelin. Experiments were designed to examine the effect of hirudin (which inactivates thrombin) and the nitrovasodilators nitroglycerin and 3-morpholinosydnonimine on the spontaneous an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.6.1768

    authors: Boulanger CM,Lüscher TF

    更新日期:1991-06-01 00:00:00

  • Heterogeneity of ATP receptors in aortic endothelial cells. Involvement of P2y and P2u receptors in inositol phosphate response.

    abstract::Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.72.3.504

    authors: Motte S,Pirotton S,Boeynaems JM

    更新日期:1993-03-01 00:00:00

  • A reliable recipe for heart cells?

    abstract::Deepak Srivastava’s group at the Gladstone Institute of Cardiovascular Disease, University of California San Francisco, reported in the August 6 issue of the journal Cell that to make heart muscle cells, all you need are three factors and some fibroblasts. But is it really that easy? ...

    journal_title:Circulation research

    pub_type: 新闻

    doi:10.1161/RES.0b013e3181ffeac0

    authors: Williams R

    更新日期:2010-10-29 00:00:00

  • At the crossroads of myocardial signaling: the role of Z-discs in intracellular signaling and cardiac function.

    abstract::Understanding the molecular interactions among components of cardiac Z-discs and their role in signaling has become pivotal in explaining long- and short-term regulation of cardiac function. In striated muscle, the ends of the thin filaments from opposing sarcomeres overlap and are cross-linked by an elaborate array o...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000116143.74830.A9

    authors: Pyle WG,Solaro RJ

    更新日期:2004-02-20 00:00:00

  • Nitric oxide is a mediator of hypoxic coronary vasodilatation. Relation to adenosine and cyclooxygenase-derived metabolites.

    abstract::Hypoxia is a potent coronary-vasodilating signal; its mechanisms are still controversial. We have assessed the possible role of nitric oxide (NO) in hypoxic coronary vasodilatation (HCVD) in isolated guinea pig hearts perfused at constant pressure. HCVD was elicited by a 1-minute 100% N2 exposure; coronary flow double...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.71.4.992

    authors: Park KH,Rubin LE,Gross SS,Levi R

    更新日期:1992-10-01 00:00:00

  • Regulation of mitogen-activated protein kinase cascade in adult rat heart preparations in vitro.

    abstract::The regulation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) was studied in freshly isolated adult rat heart preparations. In contrast to the situation in ventricular myocytes cultured from neonatal rat hearts, stimulation of MAPK activity by 1 mumol/L phorbol 12-myristate 13-acetate (PMA) was not c...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.75.5.932

    authors: Lazou A,Bogoyevitch MA,Clerk A,Fuller SJ,Marshall C J,Sugden PH

    更新日期:1994-11-01 00:00:00

  • Potassium rectifier currents differ in myocytes of endocardial and epicardial origin.

    abstract::Whole-cell voltage-clamp experiments and single-channel current recordings in cell-attached patch mode were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to compare the characteristics of inward rectifier K+ curre...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.70.1.91

    authors: Furukawa T,Kimura S,Furukawa N,Bassett AL,Myerburg RJ

    更新日期:1992-01-01 00:00:00

  • Nonuniformity of endothelial constitutive nitric oxide synthase distribution in cardiac endothelium.

    abstract::Endocardial endothelium and endothelium of coronary vessels produce NO. Histochemical methods have suggested that coronary arterial endothelial cells contain more endothelial constitutive NO synthase (ecNOS) than does coronary venous endothelium. We have further investigated the distribution of ecNOS in cardiac endoth...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.2.195

    authors: Andries LJ,Brutsaert DL,Sys SU

    更新日期:1998-02-09 00:00:00

  • Rapid attenuation ("fade") of the chronotropic response during vagal stimulation in the canine newborn. Evidence for a prominent neuropeptide Y effect.

    abstract::We studied the time-dependent changes in the response of heart rate (sinus cycle length) to 30-second trains of vagal stimulation (8 Hz), repeated every 2 minutes, in canine neonates aged 7.1 +/- 2.5 (mean +/- SD) days. The first vagal train prolonged the sinus cycle length by 58 +/- 35%, but the response was attenuat...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.69.2.406

    authors: Yamasaki S,Stolfi A,Mas MS,Fox LS,Pickoff AS

    更新日期:1991-08-01 00:00:00

  • Neurogenic inflammation in rat trachea is accompanied by increased negativity of interstitial fluid pressure.

    abstract::The present experiments were performed to investigate whether neurogenic inflammation in rat trachea (with edema formation and protein extravasation when the circulation is intact) induced by electrical field stimulation of neuropeptide-containing C fibers in the vagal nerve is accompanied by increased negativity of i...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.73.5.839

    authors: Woie K,Koller ME,Heyeraas KJ,Reed RK

    更新日期:1993-11-01 00:00:00

  • Lack of evidence for the participation of tonin in the pathogenesis of one-kidney, one-clip renovascular hypertension.

    abstract::It has been reported that immunization against tonin normalizes blood pressure, and that sialoadenectomy, during which the tonin-rich salivary glands are removed, decreases blood pressure in one-kidney, one-clip hypertension. To investigate the role of tonin on this form of hypertension further, we actively immunized ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.55.5.580

    authors: Seto S,Rabito SF,Scicli AG,Carretero OA

    更新日期:1984-11-01 00:00:00

  • Differences in the determinants of overdrive suppression between sinus rhythm and slow atrioventricular junctional rhythm.

    abstract::Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle leng...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.57.1.182

    authors: Neely BH,Urthaler F,Hageman GR

    更新日期:1985-07-01 00:00:00

  • Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes.

    abstract:RATIONALE:MicroRNAs (miRNAs) are short noncoding RNA species generated by the processing of longer precursors by the ribonucleases Drosha and Dicer. Platelets contain large amounts of miRNA that are altered by disease, in particular diabetes mellitus. OBJECTIVE:This study determined why platelet miRNA levels are atten...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.305784

    authors: Elgheznawy A,Shi L,Hu J,Wittig I,Laban H,Pircher J,Mann A,Provost P,Randriamboavonjy V,Fleming I

    更新日期:2015-07-03 00:00:00

  • Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.

    abstract:RATIONALE:Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. OBJECTIVE:This study investigated the recruitme...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.116.309301

    authors: Luther N,Shahneh F,Brähler M,Krebs F,Jäckel S,Subramaniam S,Stanger C,Schönfelder T,Kleis-Fischer B,Reinhardt C,Probst HC,Wenzel P,Schäfer K,Becker C

    更新日期:2016-12-09 00:00:00

  • Opioids in cerebrospinal fluid in hypotensive newborn pigs.

    abstract::This study was designed to determine if opioids were detectable in cerebrospinal fluid (CSF) and if these concentrations were altered by hemorrhagic hypotension. This study was further designed to determine the effects of topically administered opioids on pial arteriolar diameter during normotension and hypotension. C...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.4.922

    authors: Armstead WM,Mirro R,Busija DW,Desiderio DM,Leffler CW

    更新日期:1991-04-01 00:00:00

  • AMPKα2 Protects Against the Development of Heart Failure by Enhancing Mitophagy via PINK1 Phosphorylation.

    abstract:RATIONALE:Mitochondrial dysfunction plays an important role in heart failure (HF). However, the molecular mechanisms regulating mitochondrial functions via selective mitochondrial autophagy (mitophagy) are poorly understood. OBJECTIVE:We sought to determine the role of AMPK (AMP-activated protein kinase) in selective ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.312317

    authors: Wang B,Nie J,Wu L,Hu Y,Wen Z,Dong L,Zou MH,Chen C,Wang DW

    更新日期:2018-03-02 00:00:00

  • Oxidative posttranslational modifications mediate decreased SERCA activity and myocyte dysfunction in Galphaq-overexpressing mice.

    abstract:BACKGROUND:Myocyte contractile dysfunction occurs in pathological remodeling in association with abnormalities in calcium regulation. Mice with cardiac myocyte-specific overexpression of Galphaq develop progressive left ventricular failure associated with myocyte contractile dysfunction and calcium dysregulation. OBJE...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.110.217570

    authors: Lancel S,Qin F,Lennon SL,Zhang J,Tong X,Mazzini MJ,Kang YJ,Siwik DA,Cohen RA,Colucci WS

    更新日期:2010-07-23 00:00:00

  • Enhanced myogenic depolarization in hypertensive cerebral arterial muscle.

    abstract::We have previously demonstrated pressure-dependent membrane depolarization and action potential generation in cat cerebral arteries. It was the purpose of this study to examine and compare the membrane electrical responses to increasing transmural pressure in spontaneously hypertensive rats with those of their normote...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.57.2.319

    authors: Harder DR,Smeda J,Lombard J

    更新日期:1985-08-01 00:00:00

  • Inhibition of versican synthesis by antisense alters smooth muscle cell phenotype and induces elastic fiber formation in vitro and in neointima after vessel injury.

    abstract::The proteoglycan versican is implicated in several atherogenic events, including stimulation of vascular smooth muscle cell (VSMC) growth and migration, retention of lipoproteins, and promotion of thrombogenesis. A high content of intimal versican also correlates with a low content of elastin, suggesting an inhibitory...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000202051.28319.c8

    authors: Huang R,Merrilees MJ,Braun K,Beaumont B,Lemire J,Clowes AW,Hinek A,Wight TN

    更新日期:2006-02-17 00:00:00

  • Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes.

    abstract::3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide. However, it is unclear whether statins can exert such effects directly on cardiac myocytes and whether mitochondria...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000097262.21507.DF

    authors: Jones SP,Teshima Y,Akao M,Marbán E

    更新日期:2003-10-17 00:00:00

  • Oxidative stress-dependent sphingosine kinase-1 inhibition mediates monoamine oxidase A-associated cardiac cell apoptosis.

    abstract::The mitochondrial enzyme monoamine oxidase (MAO), its isoform MAO-A, plays a major role in reactive oxygen species-dependent cardiomyocyte apoptosis and postischemic cardiac damage. In the current study, we investigated whether sphingolipid metabolism can account for mediating MAO-A- and reactive oxygen species-depend...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000253900.66640.34

    authors: Pchejetski D,Kunduzova O,Dayon A,Calise D,Seguelas MH,Leducq N,Seif I,Parini A,Cuvillier O

    更新日期:2007-01-05 00:00:00

  • Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria.

    abstract::Although functional coupling between protein kinase Cepsilon (PKCepsilon) and mitochondria has been implicated in the genesis of cardioprotection, the signal transduction mechanisms that enable this link and the identities of the mitochondrial proteins modulated by PKCepsilon remain unknown. Based on recent evidence t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000069215.36389.8D

    authors: Baines CP,Song CX,Zheng YT,Wang GW,Zhang J,Wang OL,Guo Y,Bolli R,Cardwell EM,Ping P

    更新日期:2003-05-02 00:00:00

  • Nuclear thyroid hormone receptors in rabbit heart: reduced triiodothyronine binding in atrium compared with ventricle.

    abstract::Radiolabeled triiodothyronine (T3) binding to isolated nuclei was measured to compare the binding characteristics of the nuclear receptors in rabbit ventricular and atrial muscle cells. Scatchard analysis of the binding data yielded a maximum binding capacity of 170 +/- 20 fmol per mg DNA and apparent dissociation con...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.63.1.267

    authors: Banerjee SK,Ulrich JM,Kaldor GJ

    更新日期:1988-07-01 00:00:00

  • Critical roles for the Fas/Fas ligand system in postinfarction ventricular remodeling and heart failure.

    abstract::In myocardial infarction (MI), granulation tissue cells disappear via apoptosis to complete a final scarring with scanty cells. Blockade of this apoptosis was reported to improve post-MI ventricular remodeling and heart failure. However, the molecular biological mechanisms for the apoptosis are unknown. Fas and Fas li...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000141528.54850.bd

    authors: Li Y,Takemura G,Kosai K,Takahashi T,Okada H,Miyata S,Yuge K,Nagano S,Esaki M,Khai NC,Goto K,Mikami A,Maruyama R,Minatoguchi S,Fujiwara T,Fujiwara H

    更新日期:2004-09-17 00:00:00