Impaired VE-cadherin/beta-catenin expression mediates endothelial cell degeneration in dilated cardiomyopathy.

Abstract:

BACKGROUND:The cross-talk between vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang), and VE-cadherin coregulates endothelial cell (EC) survival. Cardiac expression of VEGF-A but not its receptor KDR is blunted in dilated cardiomyopathy (DCM). Whether VE-cadherin/Ang function is affected in DCM is unknown. METHODS AND RESULTS:The myocardial expression of VE-cadherin/beta-catenin, Ang-1, Ang-2, and their receptor Tie-2 was examined in DCM, ischemic cardiomyopathy (ICM), and in control subjects through the use of real-time RT-PCR, Western blotting, and immunocytochemistry. EC degeneration was quantified by TEM. RNA interference against VE-cadherin and VEGF deprivation and stimulation were applied to cultured DCM myocardium and human microvascular ECs to examine the interplay between VEGF, VE-cadherin/beta-catenin, and Ang-2. Analysis of tissue sections with similar rates of EC degeneration in both patient groups showed that VE-cadherin/beta-catenin expression was downregulated in DCM only (P<0.05). Although Ang-1 was not changed, Ang-2 expression was downregulated and Tie-2 protein expression was upregulated both in DCM and ICM (P<0.05). The ratio of degenerated to normal ECs was significantly higher in DCM versus ICM (P<0.05). Targeted VE-cadherin gene silencing in cultured human ECs resulted in similar degenerative effects observed in myocardial ECs of DCM patients. In vitro experiments indicated that VE-cadherin/beta-catenin expression is independent of VEGF. CONCLUSIONS:These results indicate for the first time that the EC survival is impaired in myocardium of patients with DCM involving VE-cadherin/beta-catenin, probably independent of VEGF. Targeting VE-cadherin might be of benefit to counteract the selective EC pathology in DCM.

journal_name

Circulation

journal_title

Circulation

authors

Schäfer R,Abraham D,Paulus P,Blumer R,Grimm M,Wojta J,Aharinejad S

doi

10.1161/01.CIR.0000091085.12422.19

subject

Has Abstract

pub_date

2003-09-30 00:00:00

pages

1585-91

issue

13

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000091085.12422.19

journal_volume

108

pub_type

杂志文章
  • Myocardial lactate extraction: multi-determined metabolic function.

    abstract::Myocardial lactate production indicates anaerobic metabolism resulting from hypoxia or anoxia. Clinically, myocardial lactate extraction of less than 10% has also been used as an indicator of ischemia. Sixteen healthy young male volunteers underwent coronary sinus and aterial catheterization. A coronary sinus pacing c...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.61.2.256

    authors: Gertz EW,Wisneski JA,Neese R,Houser A,Korte R,Bristow JD

    更新日期:1980-02-01 00:00:00

  • Singlet oxygen-induced arrhythmias. Dose- and light-response studies for photoactivation of rose bengal in the rat heart.

    abstract::In a study of aerobically perfused rat hearts, the in situ photoactivation (530-590 nm) of rose bengal (a process that leads to the production of singlet oxygen and superoxide) has been shown to lead to the rapid development of electrocardiographic abnormalities and arrhythmias. With rose bengal concentrations of 1,00...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.80.5.1432

    authors: Kusama Y,Bernier M,Hearse DJ

    更新日期:1989-11-01 00:00:00

  • Inhibition of inositol(1,4,5)Trisphosphate generation by endothelin-1 during postischemic reperfusion: A novel antiarrhythmic mechanism.

    abstract:BACKGROUND:Reperfusion of ischemic rat hearts in the presence of thrombin or norepinephrine but not endothelin-1 causes the generation of inositol 1,4,5-trisphosphate (Ins 1,4,5P3) and arrhythmias. The present study investigates the effect of endothelin-1 on these responses. METHODS AND RESULTS:Ins 1,4,5P3 generation ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.99.6.823

    authors: Woodcock EA,Reyes N,Jacobsen AN,Du XJ

    更新日期:1999-02-16 00:00:00

  • The angiogenic factor secretoneurin induces coronary angiogenesis in a model of myocardial infarction by stimulation of vascular endothelial growth factor signaling in endothelial cells.

    abstract:BACKGROUND:Secretoneurin is a neuropeptide located in nerve fibers along blood vessels, is upregulated by hypoxia, and induces angiogenesis. We tested the hypothesis that secretoneurin gene therapy exerts beneficial effects in a rat model of myocardial infarction and evaluated the mechanism of action on coronary endoth...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.111.076950

    authors: Albrecht-Schgoer K,Schgoer W,Holfeld J,Theurl M,Wiedemann D,Steger C,Gupta R,Semsroth S,Fischer-Colbrie R,Beer AG,Stanzl U,Huber E,Misener S,Dejaco D,Kishore R,Pachinger O,Grimm M,Bonaros N,Kirchmair R

    更新日期:2012-11-20 00:00:00

  • Regression of left ventricular hypertrophy after surgical therapy for aortic stenosis is associated with changes in extracellular matrix gene expression.

    abstract:BACKGROUND:Regression of left ventricular hypertrophy (LVH) after surgical correction for aortic stenosis is not fully understood on the molecular level. The aim of this study was to examine whether there is an association between LVH regression and extracellular matrix (ECM) gene expression. METHODS AND RESULTS:A sta...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/hc37t1.094777

    authors: Walther T,Schubert A,Falk V,Binner C,Kanev A,Bleiziffer S,Walther C,Doll N,Autschbach R,Mohr FW

    更新日期:2001-09-18 00:00:00

  • Vascular effects following homozygous disruption of p47(phox) : An essential component of NADPH oxidase.

    abstract:BACKGROUND:Evidence suggests that the vessel wall contains an oxidase similar, if not identical, to phagocytic NADPH oxidase. We tested the contribution of this specific oxidase to the progression of atherosclerosis and the regulation of blood pressure. METHODS AND RESULTS:An examination of aortic rings from wild-type...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.101.11.1234

    authors: Hsich E,Segal BH,Pagano PJ,Rey FE,Paigen B,Deleonardis J,Hoyt RF,Holland SM,Finkel T

    更新日期:2000-03-21 00:00:00

  • Preservation of donor heart function and high-energy stores by continuous perfusion with synthetic plasma at 22 degrees C.

    abstract::We evaluated high-energy phosphate (HEP) levels and the ability to perform work in rat hearts preserved by standard techniques (0.9% NaCl arrest and storage at 4 degrees C) and by continuous coronary perfusion at 22 degrees C, pH 7.25, and 55 mm Hg for 4 or 8 hr with Krebs-Henseleit buffer (KHB), modified Morgan's sol...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Novick WM,Wallace HW,Root KL,Rozanski DJ,Fuller EO

    更新日期:1986-11-01 00:00:00

  • Depressed cardiac performance after mitral valve replacement. A problem of myocardial preservation during operation.

    abstract::Our experimental studies since 1972 show that the heart is preserved best during cardiopulmonary bypass when it is in the beating, nonworking state. Results after mitral valve replacement (MVR) from 1968 to 1974 using various techniques of cardiac preservation were compared. In group I were 47 patients (1968 to 1972) ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Maloney JV Jr,Cooper N,Mulder DG,Buckberg GD

    更新日期:1975-08-01 00:00:00

  • Myocardial lesions of progressive systemic sclerosis. A cause of cardiac dysfunction.

    abstract::The nature, prevalence, functional significance, and indeed existence of myocardial disease in progressive systemic sclerosis (PSS) has been debated. In this study the clinical and pathological features of 52 autopsied patients were analyzed in an attempt to resolve these questions. A distinctive focal myocardial lesi...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.53.3.483

    authors: Bulkley BH,Ridolfi RL,Salyer WR,Hutchins GM

    更新日期:1976-03-01 00:00:00

  • Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction.

    abstract:BACKGROUND:The use of molecular biological techniques has demonstrated the importance of enteroviral infection of the myocardium in the pathogenesis of myocarditis and dilated cardiomyopathy in adults and adenovirus and enterovirus infection in children. The aim of this study was to determine the frequency of adenovira...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.99.10.1348

    authors: Pauschinger M,Bowles NE,Fuentes-Garcia FJ,Pham V,Kühl U,Schwimmbeck PL,Schultheiss HP,Towbin JA

    更新日期:1999-03-16 00:00:00

  • Downregulation of immunodetectable connexin43 and decreased gap junction size in the pathogenesis of chronic hibernation in the human left ventricle.

    abstract:BACKGROUND:The regional wall motion impairment and predisposition to arrhythmias in human ventricular hibernation may plausibly result from abnormal intercellular propagation of the depolarizing wave front. This study investigated the hypothesis that altered patterns of expression of connexin43, the principal gap junct...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.97.7.651

    authors: Kaprielian RR,Gunning M,Dupont E,Sheppard MN,Rothery SM,Underwood R,Pennell DJ,Fox K,Pepper J,Poole-Wilson PA,Severs NJ

    更新日期:1998-02-24 00:00:00

  • Gender differences in outcomes after hospital discharge from coronary artery bypass grafting.

    abstract:BACKGROUND:There are few comparative data regarding long-term nonfatal outcomes for women versus men after coronary artery bypass grafting (CABG). This study compares gender differences in cardiac events in a population of hospital survivors up to 11 years after isolated CABG surgery in Ontario, Canada. METHODS AND RE...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.105.576652

    authors: Guru V,Fremes SE,Austin PC,Blackstone EH,Tu JV

    更新日期:2006-01-31 00:00:00

  • Bilateral ductal origin of the pulmonary arteries. Systemic-pulmonary arterial anastomosis as first stage in planned total correction.

    abstract::Absence of continuity between the heart and the pulmonary arteries has the potential for total correction. When the pulmonary arteries are narrow, a palliative first stage systemic-pulmonary arterial anastomosis serves to enlarge the pulmonary arteries so that, with time, they become of adequate caliber for total corr...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.54.5.834

    authors: Todd EP,Lindsay WG,Edwards JE

    更新日期:1976-11-01 00:00:00

  • A new method for quantitation of mitral regurgitation based on color flow Doppler imaging of flow convergence proximal to regurgitant orifice.

    abstract:BACKGROUND:Imaging of the flow convergence region (FCR) proximal to a regurgitant orifice has been shown to provide a method for quantifying the regurgitant flow rate. According to the continuity principle, the FCR is constituted by concentric hemispheric isovelocity surfaces centered at the orifice. The flow rate is c...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.84.4.1481

    authors: Bargiggia GS,Tronconi L,Sahn DJ,Recusani F,Raisaro A,De Servi S,Valdes-Cruz LM,Montemartini C

    更新日期:1991-10-01 00:00:00

  • Sustained improvement after combined anterior mitral leaflet extension and myectomy in hypertrophic obstructive cardiomyopathy.

    abstract:BACKGROUND:Mitral leaflet extension (MLE) combined with septal myectomy is a new surgical approach to treat hypertrophic obstructive cardiomyopathy (HOCM) and an enlarged mitral leaflet area. The study presents the long-term clinical results and outcome of this technique. METHODS AND RESULTS:MLE entails grafting a glu...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章

    doi:10.1161/01.CIR.0000092912.57140.14

    authors: van der Lee C,Kofflard MJ,van Herwerden LA,Vletter WB,ten Cate FJ

    更新日期:2003-10-28 00:00:00

  • Carotid endarterectomy based on duplex scanning without preoperative arteriography.

    abstract::Between July 1985 and September 1987, 25 patients underwent 26 carotid endarterectomies based on an abnormal duplex scan (B-mode ultrasonography and pulsed-Doppler sound spectral analysis) indicative of severe stenosis or ulceration. Arteriography was not performed because of severe unstable angina requiring coronary ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Marshall WG Jr,Kouchoukos NT,Murphy SF,Pelate C

    更新日期:1988-09-01 00:00:00

  • Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for a role of hypoxia-inducible factor-1 in bacterial infections.

    abstract:BACKGROUND:Bartonella species are the only known bacterial pathogens causing vasculoproliferative disorders in humans (bacillary angiomatosis [BA]). Cellular and bacterial pathogenetic mechanisms underlying the induction of BA are largely unknown. METHODS AND RESULTS:Activation of hypoxia-inducible factor-1 (HIF-1), t...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000155608.07691.B7

    authors: Kempf VA,Lebiedziejewski M,Alitalo K,Wälzlein JH,Ehehalt U,Fiebig J,Huber S,Schütt B,Sander CA,Müller S,Grassl G,Yazdi AS,Brehm B,Autenrieth IB

    更新日期:2005-03-01 00:00:00

  • Mechanisms of ischemic preconditioning in rat hearts. Involvement of alpha 1B-adrenoceptors, pertussis toxin-sensitive G proteins, and protein kinase C.

    abstract:BACKGROUND:Ischemic preconditioning attenuates the effects of subsequent sustained ischemia by a mechanism involving adenosine and G proteins in several species. Adenosine is not involved in ischemic preconditioning of rat hearts, the mechanisms of which are poorly understood. METHODS AND RESULTS:Reduction of isometri...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.92.8.2259

    authors: Hu K,Nattel S

    更新日期:1995-10-15 00:00:00

  • Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function.

    abstract:BACKGROUND:Central aortic pressures and waveform convey important information about cardiovascular status, but direct measurements are invasive. Peripheral pressures can be measured noninvasively, and although they often differ substantially from central pressures, they may be mathematically transformed to approximate ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.95.7.1827

    authors: Chen CH,Nevo E,Fetics B,Pak PH,Yin FC,Maughan WL,Kass DA

    更新日期:1997-04-01 00:00:00

  • Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage.

    abstract:BACKGROUND:Aldosterone and angiotensin (Ang) II both may cause organ damage. Circulating aldosterone is produced in the adrenals; however, local cardiac synthesis has been reported. Aldosterone concentrations depend on the activity of aldosterone synthase (CYP11B2). We tested the hypothesis that reducing aldosterone by...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.104.521625

    authors: Fiebeler A,Nussberger J,Shagdarsuren E,Rong S,Hilfenhaus G,Al-Saadi N,Dechend R,Wellner M,Meiners S,Maser-Gluth C,Jeng AY,Webb RL,Luft FC,Muller DN

    更新日期:2005-06-14 00:00:00

  • Role of Rho-associated kinase in neointima formation after vascular injury.

    abstract:BACKGROUND:The Rho/Rho-associated kinase (Rho-kinase) system is implicated in various cellular functions, including migration, proliferation, and apoptosis. Because a possible role of the system is suggested in neointima formation after vascular injury, we sought to examine whether a new specific Rho-kinase inhibitor, ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.103.2.284

    authors: Shibata R,Kai H,Seki Y,Kato S,Morimatsu M,Kaibuchi K,Imaizumi T

    更新日期:2001-01-16 00:00:00

  • Hypoxic response contributes to altered gene expression and precapillary pulmonary hypertension in patients with sickle cell disease.

    abstract:BACKGROUND:We postulated that the hypoxic response in sickle cell disease (SCD) contributes to altered gene expression and pulmonary hypertension, a complication associated with early mortality. METHODS AND RESULTS:To identify genes regulated by the hypoxic response and not other effects of chronic anemia, we compared...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.113.005296

    authors: Zhang X,Zhang W,Ma SF,Desai AA,Saraf S,Miasniakova G,Sergueeva A,Ammosova T,Xu M,Nekhai S,Abbasi T,Casanova NG,Steinberg MH,Baldwin CT,Sebastiani P,Prchal JT,Kittles R,Garcia JG,Machado RF,Gordeuk VR

    更新日期:2014-04-22 00:00:00

  • Role of ATP-sensitive K+ channel on ECG ST segment elevation during a bout of myocardial ischemia. A study on epicardial mapping in dogs.

    abstract:BACKGROUND:ATP-sensitive K+ channels are activated when the myocardium becomes ischemic. However, the role of the ATP-sensitive K+ current in the emergence of ECG ST changes during ischemia remained unclarified. METHODS AND RESULTS:The left anterior descending coronary artery (LAD) was cannulated and perfused with art...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.88.4.1845

    authors: Kubota I,Yamaki M,Shibata T,Ikeno E,Hosoya Y,Tomoike H

    更新日期:1993-10-01 00:00:00

  • Adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction in Costa Rica.

    abstract:BACKGROUND:Alpha-linolenic acid may protect against cardiovascular disease. We examined the association between adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction (MI) in a population-based case-control study in Costa Rica. METHODS AND RESULTS:The 482 case patients with a first nonfatal acute...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000058165.81208.C6

    authors: Baylin A,Kabagambe EK,Ascherio A,Spiegelman D,Campos H

    更新日期:2003-04-01 00:00:00

  • Molecular genetics of lipoprotein disorders.

    abstract::These types of studies lay the foundation for understanding the human apolipoproteins at the genetic level. In addition, through a few specific examples, we have already shown evidence at the DNA level that lesions in apolipoprotein genes can play a role in human atherosclerosis. This work is in its infancy, but we ho...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.69.6.1190

    authors: Breslow JL

    更新日期:1984-06-01 00:00:00

  • Simultaneous autologous transplantation of cocultured mesenchymal stem cells and skeletal myoblasts improves ventricular function in a murine model of Chagas disease.

    abstract:BACKGROUND:Cellular transplantation is emerging as a promising strategy for the treatment of postinfarction ventricular dysfunction. Whether its beneficial effects can be extended to other cardiomyopathies remains an unexplored question. We evaluated the histological and functional effects of simultaneous autologous tr...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.105.000646

    authors: Guarita-Souza LC,Carvalho KA,Woitowicz V,Rebelatto C,Senegaglia A,Hansen P,Miyague N,Francisco JC,Olandoski M,Faria-Neto JR,Brofman P

    更新日期:2006-07-04 00:00:00

  • High density lipoprotein metabolism in endurance athletes and sedentary men.

    abstract:BACKGROUND:Endurance athletes have higher high density lipoprotein (HDL) concentrations than sedentary controls. To examine the mechanism for this effect, we compared HDL apoprotein metabolism in 10 endurance athletes aged 34 +/- 6 years (mean +/- SD) and 10 sedentary men aged 36 +/- 8 years. METHODS AND RESULTS:Subje...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.84.1.140

    authors: Thompson PD,Cullinane EM,Sady SP,Flynn MM,Chenevert CB,Herbert PN

    更新日期:1991-07-01 00:00:00

  • Congenital heart block in newborns of mothers with connective tissue disease.

    abstract::Of 22 children with congenital complete heart block (CCHB) available for study, 14 (63.6%) were born to 11 mothers with clinical or laboratory evidence of connective tissue disease, primarily lupus erythematosus (LE). Seven mothers had both clinical and laboratory evidence of disease while four had only positive labor...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.56.1.82

    authors: McCue CM,Mantakas ME,Tingelstad JB,Ruddy S

    更新日期:1977-07-01 00:00:00

  • Volumetric analysis of in-stent intimal hyperplasia in diabetic patients treated with or without abciximab: results of the Diabetes Abciximab steNT Evaluation (DANTE) randomized trial.

    abstract:BACKGROUND:In diabetic patients in the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, abciximab reduced target vessel revascularization by approximately 50% compared with placebo. Whether this is a result of a lower restenosis rate caused by inhibition of intimal hyperplasia remains to be defi...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1161/01.CIR.0000116752.12261.D4

    authors: Chaves AJ,Sousa AG,Mattos LA,Abizaid A,Staico R,Feres F,Centemero M,Tanajura LF,Abizaid A,Pinto I,Maldonado G,Seixas A,Costa MA,Paes A,Mintz GS,Sousa JE

    更新日期:2004-02-24 00:00:00

  • Importance of endogenous adenosine during ischemia and reperfusion in neonatal porcine hearts.

    abstract:BACKGROUND:Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. METHODS AND RESULTS:Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.96.9.3094

    authors: Sommerschild HT,Grund F,Offstad J,Jynge P,Ilebekk A,Kirkebøen KA

    更新日期:1997-11-04 00:00:00