Ablation of Nkx2-5 at mid-embryonic stage results in premature lethality and cardiac malformation.

Abstract:

AIMS:Human congenital heart disease linked to mutations in the homeobox transcription factor, NKX2-5, is characterized by cardiac anomalies, including atrial and ventricular septal defects as well as conduction and occasional defects in contractility. In the mouse, homozygous germline deletion of Nkx2-5 gene results in death around E10.5. It is, however, not established whether Nkx2-5 is necessary for cardiac development beyond this embryonic stage. Because human NKX2-5 mutations are related to septum secundum type atrial septal defects (ASD), we hypothesized that Nkx2-5 deficiency during the processes of septum secundum formation may cause cardiac anomalies; thus, we analysed mice with tamoxifen-inducible Nkx2-5 ablation beginning at E12.5 when the septum secundum starts to develop. METHODS AND RESULTS:Using tamoxifen-inducible Nkx2-5 gene-targeted mice, this study demonstrates that Nkx2-5 ablation beginning at E12.5 results in embryonic death by E17.5. Analysis of mutant embryos at E16.5 shows arrhythmias, contraction defects, and cardiac malformations, including ASD. Quantitative measurements using serial section histology and three-dimensional reconstruction demonstrate growth retardation of the septum secundum and enlarged foramen ovale in Nkx2-5-ablated embryos. Functional cardiac defects may be attributed to abnormal expression of transcripts critical for conduction and contraction, including cardiac voltage-gated Na(+) channel pore-forming α-subunit (Na(v)1.5-α), gap junction protein connexin40, cardiac myosin light chain kinase, and sarcolipin within 4 days after tamoxifen injection. CONCLUSION:Nkx2-5 is necessary for survival after the mid-embryonic stage for cardiac function and formation by regulating the expression of its downstream target genes.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Terada R,Warren S,Lu JT,Chien KR,Wessels A,Kasahara H

doi

10.1093/cvr/cvr037

subject

Has Abstract

pub_date

2011-07-15 00:00:00

pages

289-99

issue

2

eissn

0008-6363

issn

1755-3245

pii

cvr037

journal_volume

91

pub_type

杂志文章
  • SR calcium handling and calcium after-transients in a rabbit model of heart failure.

    abstract:OBJECTIVE:After-depolarization associated arrhythmias are frequently observed in heart failure and associated with spontaneous calcium release from sarcoplasmic reticulum (SR), calcium after-transients. We hypothesize that disturbed SR calcium handling underlies calcium after-transients in heart failure (HF). METHODS:...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00854-4

    authors: Baartscheer A,Schumacher CA,Belterman CN,Coronel R,Fiolet JW

    更新日期:2003-04-01 00:00:00

  • Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits.

    abstract:AIMS:ATP sensitive K(+) channels (K(ATP)) sense adenine nucleotide concentrations and thus couple the metabolic state of the cell to membrane potential. The hetero-octameric complex of a sulphonylurea receptor (SUR2B) and an inwardly rectifying K(+) channel (Kir6.1) and the corresponding native channel in smooth muscle...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvn138

    authors: Farzaneh T,Tinker A

    更新日期:2008-09-01 00:00:00

  • Vascularizing the heart.

    abstract::As the developing heart grows and the chamber walls thicken, passive diffusion of oxygen and nutrients is replaced by a vascular plexus which remodels and expands to form a mature coronary vascular system. The coronary arteries and veins ensure the continued development of the heart and facilitate cardiac output with ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvr035

    authors: Riley PR,Smart N

    更新日期:2011-07-15 00:00:00

  • Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia.

    abstract::Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Most previous investigations focused on the role of homocysteine as direct pathogenetic factor for these adverse vascular events. However, the exact pathophysiological mechanism is still unknown. In this review we discuss the hypothesis tha...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(03)00462-0

    authors: Riksen NP,Rongen GA,Blom HJ,Russel FG,Boers GH,Smits P

    更新日期:2003-08-01 00:00:00

  • Microangiographic assessment of collateral vessel formation following direct gene transfer of vascular endothelial growth factor in rats.

    abstract:OBJECTIVE:The development of collateral microvessels following therapeutic angiogenesis with vascular endothelial growth factor (VEGF) was investigated using a new system of microangiography that employs monochromatic synchrotron radiation (SR) and a high definition video system to visualize arteries with a spatial res...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(97)00157-0

    authors: Takeshita S,Isshiki T,Mori H,Tanaka E,Tanaka A,Umetani K,Eto K,Miyazawa Y,Ochiai M,Sato T

    更新日期:1997-09-01 00:00:00

  • Electrophysiological effects of labetolol on rabbit atrial, ventricular and Purkinje cells, in normoxia and hypoxia.

    abstract::Labetolol, which blocks both alpha and beta-adrenoceptors, was found to have direct actions on cardiac muscle which could themselves be antiarrhythmic. It depressed the maximum rate of depolarisation, and reduced conduction velocity, in atrial and ventricular muscle and in Purkinje cells, implying restriction of fast ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/16.5.233

    authors: Vaughn Williams EM,Millar JS,Campbell TJ

    更新日期:1982-05-01 00:00:00

  • A comparative study on ischaemia- or anoxia-induced impairment of myocytic structure and cardiac function in the isolated, isovolumicly-contracting, perfused rat heart.

    abstract::Impairment of contractile function and extent of release of several intracellular marker enzymes and DNA were studied in isolated perfused rat hearts after low-flow (0.16 ml . min-1) ischaemia followed by 2 h of reperfusion and after anoxia followed by 2 h of reoxygenation. After varying periods of ischaemia or anoxia...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/18.12.768

    authors: van der Laarse A,Altona JC,Zoet AC,Oemrawsingh P,van Dijkman PR

    更新日期:1984-12-01 00:00:00

  • Keeping up the balance: role of HDACs in cardiac proteostasis and therapeutic implications for atrial fibrillation.

    abstract::Cardiomyocytes are long-lived post-mitotic cells with limited regenerative capacity. Proper cardiomyocyte function depends critically on the maintenance of a healthy homeostasis of protein expression, folding, assembly, trafficking, function, and degradation, together commonly referred to as proteostasis. Impairment o...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvv265

    authors: Zhang D,Hu X,Henning RH,Brundel BJ

    更新日期:2016-04-01 00:00:00

  • Augmentation of late sodium current unmasks the proarrhythmic effects of amiodarone.

    abstract:AIM:Clinical use of amiodarone is associated with occasional development of torsade de pointes (TdP). However, preclinical models have failed to demonstrate the proarrhythmic potential of amiodarone. The objective of this study was to reveal and explain the pro- and anti-arrhythmic effects of acute exposure to amiodaro...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvm069

    authors: Wu L,Rajamani S,Shryock JC,Li H,Ruskin J,Antzelevitch C,Belardinelli L

    更新日期:2008-02-01 00:00:00

  • Effects of chronic PGHS-2 inhibition on PGHS-dependent vasoconstriction in the aged female rat.

    abstract:OBJECTIVE:In menopause, aging and decreased estrogen levels are risk factors contributing to impaired vascular function. Previously, in a young ovariectomized rat model, we demonstrated an increase in prostaglandin H synthase (PGHS)-dependent vasoconstriction that could be prevented by estrogen replacement. Subsequentl...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2003.11.009

    authors: Armstrong SJ,Xu Y,Davidge ST

    更新日期:2004-02-01 00:00:00

  • Exchange protein activated by cyclic-adenosine monophosphate (Epac) regulates atrial fibroblast function and controls cardiac remodelling.

    abstract:Aims:Heart failure (HF) produces left atrial (LA)-selective fibrosis and promotes atrial fibrillation. HF also causes adrenergic activation, which contributes to remodelling via a variety of signalling molecules, including the exchange protein activated by cAMP (Epac). Here, we evaluate the effects of Epac1-signalling ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvy173

    authors: Surinkaew S,Aflaki M,Takawale A,Chen Y,Qi XY,Gillis MA,Shi YF,Tardif JC,Chattipakorn N,Nattel S

    更新日期:2019-01-01 00:00:00

  • Impairment of left ventricular function by acute cardiac lymphatic obstruction.

    abstract:OBJECTIVES:We performed the following study to define the effects of acute cardiac lymphatic obstruction on left ventricular (LV) systolic and diastolic function. METHODS:Cardiac lymphatic obstruction was created in 8 pentobarbital-anesthetized dogs by identifying (Evans blue) and ligating the right and left epicardia...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(96)00177-0

    authors: Ludwig LL,Schertel ER,Pratt JW,McClure DE,Ying AJ,Heck CF,Myerowitz PD

    更新日期:1997-01-01 00:00:00

  • Effect of physiological mechanical perturbations on intact human myocardial repolarization.

    abstract:OBJECTIVE:The objective of this study was to investigate the relationship between acute decreases in right ventricular volume during Valsalva strain (with resultant changes in autonomic neural tone) and measures of local endocardial repolarization time independent of heart rate and autonomic neural tone. METHODS:Patie...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(99)00261-8

    authors: Nanthakumar K,Dorian P,Paquette M,Hutchison S,Andrews J,Newman D

    更新日期:2000-01-14 00:00:00

  • Bestrophin is important for the rhythmic but not the tonic contraction in rat mesenteric small arteries.

    abstract:AIMS:We have previously characterized a cGMP-dependent Ca(2+)-activated Cl(-) current in vascular smooth muscle cells (SMCs) and have shown its dependence on bestrophin-3 expression. We hypothesize that this current is important for synchronization of SMCs in the vascular wall. In the present study, we aimed to test th...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvr111

    authors: Broegger T,Jacobsen JC,Secher Dam V,Boedtkjer DM,Kold-Petersen H,Pedersen FS,Aalkjaer C,Matchkov VV

    更新日期:2011-09-01 00:00:00

  • Growth and differentiation of rat bone marrow stromal cells: does 5-azacytidine trigger their cardiomyogenic differentiation?

    abstract:OBJECTIVE:The potential use of bone marrow stromal cells (MSCs) as a cellular therapy for chronic cardiac diseases relies on the ability of the cell to replicate extensively in vitro and to give rise to myogenic cells that can replace the damaged cardiomyocytes. For this reason the present study investigated the replic...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(03)00265-7

    authors: Liu Y,Song J,Liu W,Wan Y,Chen X,Hu C

    更新日期:2003-05-01 00:00:00

  • miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis pathways.

    abstract:Aims:Atherosclerosis is an inflammatory disease wherein cholesterol-loaded macrophages play a major role. MicroRNAs and microparticles propagate inflammatory pathways and are involved in cardiovascular disease. We aimed to screen and validate circulating microRNAs correlated with atherosclerosis development in humans, ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvx157

    authors: Ceolotto G,Giannella A,Albiero M,Kuppusamy M,Radu C,Simioni P,Garlaschelli K,Baragetti A,Catapano AL,Iori E,Fadini GP,Avogaro A,Vigili de Kreutzenberg S

    更新日期:2017-11-01 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

  • Strategies for directing the differentiation of stem cells into the cardiomyogenic lineage in vitro.

    abstract::Most studies on stem cell transplantation therapy on myocardially infarcted animal models and phase-I human clinical trials have focused on the use of undifferentiated stem cells. There is a strong possibility that some degree of cardiomyogenic differentiation of stem cells in vitro prior to transplantation would resu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2003.12.022

    authors: Heng BC,Haider HKh,Sim EK,Cao T,Ng SC

    更新日期:2004-04-01 00:00:00

  • RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node.

    abstract:Aims:RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvx104

    authors: Vicente-Steijn R,Kelder TP,Tertoolen LG,Wisse LJ,Pijnappels DA,Poelmann RE,Schalij MJ,deRuiter MC,Gittenberger-de Groot AC,Jongbloed MRM

    更新日期:2017-08-01 00:00:00

  • Constitutive glycogen synthase kinase-3alpha/beta activity protects against chronic beta-adrenergic remodelling of the heart.

    abstract:AIMS:Glycogen synthase kinase 3 (GSK-3) signalling is implicated in the growth of the heart during development and in response to stress. However, its precise role remains unclear. We set out to characterize developmental growth and response to chronic isoproterenol (ISO) stress in knockin (KI) mice lacking the critica...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvq061

    authors: Webb IG,Nishino Y,Clark JE,Murdoch C,Walker SJ,Makowski MR,Botnar RM,Redwood SR,Shah AM,Marber MS

    更新日期:2010-08-01 00:00:00

  • Emerging role of G protein-coupled receptors in microvascular myogenic tone.

    abstract::Blood flow autoregulation results from the ability of resistance arteries to reduce or increase their diameters in response to changes in intravascular pressure. The mechanism by which arteries maintain a constant blood flow to organs over a range of pressures relies on this myogenic response, which defines the intrin...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvs152

    authors: Kauffenstein G,Laher I,Matrougui K,Guérineau NC,Henrion D

    更新日期:2012-07-15 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

  • Overlapping and distinct roles for PI3Kbeta and gamma isoforms in S1P-induced migration of human and mouse endothelial cells.

    abstract:AIMS:Sphingosine-1-phosphate (S1P), a key regulator of vascular homeostasis and angiogenesis, promotes endothelial cell migration via stimulation of phosphoinositide 3-kinase (PI3K). The aim of this study was to identify the role of PI3Kbeta and gamma isoforms and their downstream effector pathways in mediating endothe...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvn159

    authors: Heller R,Chang Q,Ehrlich G,Hsieh SN,Schoenwaelder SM,Kuhlencordt PJ,Preissner KT,Hirsch E,Wetzker R

    更新日期:2008-10-01 00:00:00

  • Importance of endothelial NF-κB signalling in vascular remodelling and aortic aneurysm formation.

    abstract:AIMS:Vascular remodelling and aortic aneurysm formation are induced mainly by inflammatory responses in the adventitia and media. However, relatively little is known about the mechanistic significance of endothelium in the pathogenesis of these vascular disorders. The transcription factor nuclear factor-kappa B (NF-κB)...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvs298

    authors: Saito T,Hasegawa Y,Ishigaki Y,Yamada T,Gao J,Imai J,Uno K,Kaneko K,Ogihara T,Shimosawa T,Asano T,Fujita T,Oka Y,Katagiri H

    更新日期:2013-01-01 00:00:00

  • Functional role of collateral flow in the ischaemic dog heart.

    abstract::Studies were carried out in four different canine preparations to determine the effect of collateral flow on early changes induced by acute segmental ischaemia. The results of these experiments indicated that collateral flow provided a limited and variable amount of protection. When collateral flow was eliminated, myo...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/12.5.309

    authors: Koke JR,Bittar N

    更新日期:1978-05-01 00:00:00

  • Anti-platelet drugs attenuate the expansion of circulating CD14highCD16+ monocytes under pro-inflammatory conditions.

    abstract:AIMS:Levels of circulating CD14(high)CD16(+) monocytes increase in atherosclerotic patients and are predictive of future cardiovascular events. Platelet activation has been identified as a crucial determinant in the acquisition of a CD16(+) phenotype by classical CD14(high)CD16(-) cells. We tested the hypothesis that a...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/cvr/cvw089

    authors: Layne K,Di Giosia P,Ferro A,Passacquale G

    更新日期:2016-07-01 00:00:00

  • The contribution of ionic currents to changes in refractoriness of human atrial myocytes associated with chronic atrial fibrillation.

    abstract:OBJECTIVE:To investigate changes in human atrial single cell functional electrophysiological properties associated with chronic atrial fibrillation (AF), and the contribution to these of accompanying ion current changes. METHODS:The whole cell patch clamp technique was used to record action potentials, the effective r...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(01)00380-7

    authors: Workman AJ,Kane KA,Rankin AC

    更新日期:2001-11-01 00:00:00

  • Mitochondria in vascular disease.

    abstract::Mitochondria are often regarded as the powerhouse of the cell by generating the ultimate energy transfer molecule, ATP, which is required for a multitude of cellular processes. However, the role of mitochondria goes beyond their capacity to create molecular fuel, to include the generation of reactive oxygen species, t...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvs111

    authors: Yu E,Mercer J,Bennett M

    更新日期:2012-07-15 00:00:00

  • Evaluation of the effect of metoprolol on energy metabolism in the ischaemic myocardium in relation to regional myocardial blood flow.

    abstract::To evaluate the effect of beta blockade on energy metabolism in ischaemic myocardium metoprolol tartrate in doses of 0.2 or 0.5 mg.kg-1 or saline was injected into 24 anaesthetised dogs 20 min after coronary ligation. Regional myocardial blood flow was measured by the hydrogen gas clearance method, and the heart rate ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/21.9.660

    authors: Nanki M,Itoh K,Matsubara T,Nishimura K,Kambe T,Sugiyama S,Ozawa T,Sakamoto N

    更新日期:1987-09-01 00:00:00

  • Impaired P2X signalling pathways in renal microvascular myocytes in genetic hypertension.

    abstract:AIMS:P2X receptors (P2XRs) mediate sympathetic control and autoregulation of renal circulation triggering preglomerular vasoconstriction, which protects glomeruli from elevated pressures. Although previous studies established a casual link between glomerular susceptibility to hypertensive injury and decreased preglomer...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvu249

    authors: Gordienko D,Povstyan O,Sukhanova K,Raphaël M,Harhun M,Dyskina Y,Lehen'kyi V,Jama A,Lu ZL,Skryma R,Prevarskaya N

    更新日期:2015-02-01 00:00:00