BMP-7 attenuates left ventricular remodelling under pressure overload and facilitates reverse remodelling and functional recovery.

Abstract:

AIMS:TGF-β regulates tissue fibrosis: TGF-β promotes fibrosis, whereas bone morphogenetic protein (BMP)-7 is antifibrotic. To demonstrate that (i) left ventricular (LV) remodelling after pressure overload is associated with disequilibrium in the signalling mediated by these cytokines, and (ii) BMP-7 exerts beneficial effects on LV remodelling and reverse remodelling. METHODS AND RESULTS:We studied patients with aortic stenosis (AS) and mice subjected to transverse aortic constriction (TAC) and TAC release (de-TAC). LV morphology and function were assessed by echocardiography. LV biopsies were analysed by qPCR, immunoblotting, and histology. Pressure overload reduced BMP-7 and pSmad1/5/8 and increased TGF-β and pSmad2/3 in AS patients and TAC mice. BMP-7 correlated inversely with collagen, fibronectin, and β-MHC expressions, and with hypertrophy and diastolic dysfunction, and directly with the systolic function. Multiple linear regression disclosed BMP-7 and TGF-β as hypertrophy predictors, negative and positive, respectively. BMP-7 prevented TGF-β-elicited hypertrophic program in cardiomyocytes, and Col1A1 promoter activity in NIH-3T3 fibroblasts. The treatment of TAC mice with rBMP-7 attenuated the development of structural damage and dysfunction, and halted ongoing remodelling. The reverse remodelling after pressure overload release was facilitated by rBMP-7, and hampered by disrupting BMP-7 function using a neutralizing antibody or genetic deletion. CONCLUSION:The disequilibrium between BMP-7 and TGF-β signals plays a relevant role in the LV remodelling response to haemodynamic stress in TAC mice and AS patients. Our observations may provide new important insights aimed at developing novel therapies designed to prevent, halt, or reverse LV pathological remodelling in pressure overload cardiomyopathy.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Merino D,Villar AV,García R,Tramullas M,Ruiz L,Ribas C,Cabezudo S,Nistal JF,Hurlé MA

doi

10.1093/cvr/cvw076

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

331-45

issue

3

eissn

0008-6363

issn

1755-3245

pii

cvw076

journal_volume

110

pub_type

杂志文章
  • Effect of circulation time on plasma high density lipoprotein cholesterol in rats.

    abstract::The effect of circulation time on plasma high density lipoprotein cholesterol concentrations was investigated in 20 male Wistar rats injected with alcohol, stressed with lighting, or fed a high fat diet. Circulation time was measured during anaesthesia with a computerised dichromatic earpiece densitometer. Indocyanine...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/22.5.368

    authors: Ishizuka T

    更新日期:1988-05-01 00:00:00

  • Sympathetic outflow to the hand in patients with Raynaud's phenomenon.

    abstract::Microelectrode recordings of skin nerve sympathetic activity were made in the median nerve supplying the right hand of nine patients with Raynaud's phenomenon and 10 control subjects. With subjects warmed up (finger temperature 33 to 34 degrees C) different manoeuvres were used to evoke strong, single sympathetic burs...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/19.5.249

    authors: Fagius J,Blumberg H

    更新日期:1985-05-01 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

  • High Sodium Intake, Glomerular Hyperfiltration and Protein Catabolism in Patients with Essential Hypertension.

    abstract:AIMS:A blood pressure-independent metabolic shift toward a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvaa205

    authors: Rossitto G,Maiolino G,Lerco S,Ceolotto G,Blackburn G,Mary S,Antonelli G,Berton C,Bisogni V,Cesari M,Seccia TM,Lenzini L,Pinato A,Montezano A,Touyz RM,Petrie MC,Daly R,Welsh P,Plebani M,Rossi GP,Delles C

    更新日期:2020-07-16 00:00:00

  • Segmental volume distensibility of the canine thoracic aorta in vivo.

    abstract::Segments of the canine ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta were instrumented with ultrasonic dimension gauges and a cathetertip manometer simultaneously to measure changes in segment diameter, length, and intravascular pressure. Volume distensibility (EV) was calculat...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/22.6.385

    authors: Gentile BJ,Gross DR,Chuong CJ,Hwang NH

    更新日期:1988-06-01 00:00:00

  • Angiotensin converting enzyme and kininase-II-like activities in cultured valvular interstitial cells of the rat heart.

    abstract:OBJECTIVE:The function of angiotensin converting enzyme (ACE) at cell sites of high collagen turnover, such as heart valves, is uncertain. The aim of this study was to assess ACE and kininase-II-like activities and collagen turnover in cultured valvular interstitial cells of the adult rat heart. METHODS:The valvular i...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Katwa LC,Ratajska A,Cleutjens JP,Sun Y,Zhou G,Lee SJ,Weber KT

    更新日期:1995-01-01 00:00:00

  • Forearm arterial compliance: a new measure of arterial compliance?

    abstract::This study has investigated the origin of the pulsatile expansion of the forearm recorded by the amplification of the pulsatile signal derived from a mercury in rubber plethysmograph. Venous occlusion to pressures of 40 mmHg had no effect on the amplitude of the volume pulse, suggesting that the volume pulse originate...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/18.11.651

    authors: Fitchett DH

    更新日期:1984-11-01 00:00:00

  • Developmental changes of connexin40 and connexin43 mRNA distribution patterns in the rat heart.

    abstract:OBJECTIVES:Gap junctions have been demonstrated ultrastructurally in cardiac regions where connexin40 (Cx40) and connexin43 (Cx43) protein could not be detected immunohistochemically. We investigated therefore the distribution of their mRNAs with more sensitive techniques. METHODS:In situ hybridizations with Cx40 and ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/0008-6363(96)00131-9

    authors: Van Kempen MJ,Vermeulen JL,Moorman AF,Gros D,Paul DL,Lamers WH

    更新日期:1996-11-01 00:00:00

  • Regulation of contractile proteins in diabetic heart.

    abstract::Diabetes is one of the most prevalent chronic conditions that has a high association with death from cardiovascular disease(s). An impaired cardiac function independent of vascular disease suggests the existence of a primary myocardial defect in diabetes mellitus. We and others have documented that myocardial performa...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(97)00059-x

    authors: Malhotra A,Sanghi V

    更新日期:1997-04-01 00:00:00

  • Relationship between placental blood flow and combined ventricular output with gestational age in normal human fetus.

    abstract:STUDY OBJECTIVE:The aim was to quantify the changes in placental blood flow and combined ventricular output with gestational age in normal human fetuses to determine the percentage of total cardiac output that placental blood flow represented, and whether this changed with age. DESIGN:Two dimensional echocardiographic...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/25.7.603

    authors: Sutton MG,Plappert T,Doubilet P

    更新日期:1991-07-01 00:00:00

  • A novel therapeutic peptide targeting myocardial reperfusion injury.

    abstract:AIMS:Regulated cell death is a main contributor of myocardial ischaemia-reperfusion (IR) injury during acute myocardial infarction. In this context, targeting apoptosis could be a potent therapeutical strategy. In a previous study, we showed that DAXX (death-associated protein) was essential for transducing the FAS-dep...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvz145

    authors: Boisguérin P,Covinhes A,Gallot L,Barrère C,Vincent A,Busson M,Piot C,Nargeot J,Lebleu B,Barrère-Lemaire S

    更新日期:2020-03-01 00:00:00

  • Susceptibility genes and modifiers for cardiac arrhythmias.

    abstract::The last decade has seen a dramatic increase in the understanding of the molecular basis of arrhythmias. Much of this new information has been driven by genetic studies that focused on rare, monogenic arrhythmia syndromes that were accompanied or followed by cellular electrophysiological or biochemical studies. The ma...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2005.04.005

    authors: Kääb S,Schulze-Bahr E

    更新日期:2005-08-15 00:00:00

  • Strategies to achieve coronary arterial plaque stabilization.

    abstract::Acute coronary syndromes result from fissure, erosion or rupture of a vulnerable atherosclerotic plaque. The characteristics of a vulnerable plaque include a large lipid pool, an abundance of inflammatory cells and mediators, a reduced smooth muscle cell and collagen content and a thin overlying fibrous cap. Potential...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(98)00279-x

    authors: Rabbani R,Topol EJ

    更新日期:1999-02-01 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

  • Functional heterogeneity of oxygen supply-consumption ratio in the heart.

    abstract::In this review, the regional heterogeneity of the oxygen supply-consumption ratio within the heart is discussed. This is an important functional parameter because it determines whether regions within the heart are normoxic or dysoxic. Although the heterogeneity of the supply side of oxygen has been primarily described...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(99)00231-x

    authors: Zuurbier CJ,van Iterson M,Ince C

    更新日期:1999-12-01 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

  • Functional crosstalk between cardiac fibroblasts and adult cardiomyocytes by soluble mediators.

    abstract:AIMS:Crosstalk between cardiomyocytes and fibroblasts in physiological conditions and during disease remains poorly defined. Previous studies have shown that fibroblasts and myocytes interact via paracrine communication, but several experimental confounding factors, including the use of immature myocytes and the induct...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvu264

    authors: Cartledge JE,Kane C,Dias P,Tesfom M,Clarke L,Mckee B,Al Ayoubi S,Chester A,Yacoub MH,Camelliti P,Terracciano CM

    更新日期:2015-03-01 00:00:00

  • Capitalizing on diversity: an integrative approach towards the multiplicity of cellular mechanisms underlying myogenic responsiveness.

    abstract::The intrinsic ability of resistance arteries to respond to transmural pressure is the single most important determinant of their function. Despite an ever-growing catalogue of signalling pathways that underlie the myogenic response, it remains an enigmatic mechanism. The myogenic response's mechanistic diversity has l...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvs345

    authors: Lidington D,Schubert R,Bolz SS

    更新日期:2013-03-01 00:00:00

  • Adenosine inhibits norepinephrine release in the postischemic rat heart: the mechanism of neuronal stunning.

    abstract:OBJECTIVE:Numerous studies support the concept of impaired postischemic sympathetic neurotransmission in the heart. We hypothesized that postischemic neuronal dysfunction (neuronal stunning) is caused by a transient suppression of exocytotic norepinephrine (NE) release from sympathetic nerve terminals. Furthermore, we ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00309-6

    authors: Burgdorf C,Richardt D,Kurz T,Seyfarth M,Jain D,Katus HA,Richardt G

    更新日期:2001-03-01 00:00:00

  • Localisation of neuropeptide Y in nerves of the rat cardiovascular system and the effect of 6-hydroxydopamine.

    abstract::The distribution of neuropeptide Y (NPY) in the rat cardiovascular system has been examined by radioimmunoassay, chromatographic analysis of tissue extracts, and immunocytochemistry. High concentrations of NPY were identified throughout the heart and within the major blood vessels of the rat in particular in the renal...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/19.9.570

    authors: Allen JM,Polak JM,Rodrigo J,Darcy K,Bloom SR

    更新日期:1985-09-01 00:00:00

  • Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes.

    abstract:AIMS:Hydrogen sulphide (H(2)S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H(2)S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H(2...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvn140

    authors: Sun YG,Cao YX,Wang WW,Ma SF,Yao T,Zhu YC

    更新日期:2008-09-01 00:00:00

  • From genes to channels: normal mechanisms.

    abstract::Electrophysiologic remodeling is a process whereby heart disease alters the electrophysiologic properties of cardiac tissue. These alterations, in turn, can cause or exacerbate disease-related arrhythmias. Ion channels are the fundamental molecular units underlying cardiac electrophysiology, and it therefore follows t...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(99)00063-2

    authors: Roden DM,Kupershmidt S

    更新日期:1999-05-01 00:00:00

  • Endothelial injury of arteries following catheterisation with polyethylene tubes: experimental studies on rabbit aorta using the Seldinger technique.

    abstract::The effect of catheterisation on the rabbit aortic wall is investigated employing a technique identical to that used for continuous monitoring of blood pressure in humans. The catheters were introduced into the aorta through the right femoral artery of the rabbit using the Seldinger technique, except that the catheter...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/13.9.541

    authors: Madsen JK,Garbarsch C,Nielsen PE

    更新日期:1979-09-01 00:00:00

  • A novel fibroblast growth factor-1 ligand with reduced heparin binding protects the heart against ischemia-reperfusion injury in the presence of heparin co-administration.

    abstract:Aims:Fibroblast growth factor 1 (FGF1), a heparin/heparan sulfate-binding growth factor, is a potent cardioprotective agent against myocardial infarction (MI). The impact of heparin, the standard of care for MI patients entering the emergency room, on cardioprotective effects of FGF1 is unknown, however. Methods and r...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvx165

    authors: Huang C,Liu Y,Beenken A,Jiang L,Gao X,Huang Z,Hsu A,Gross GJ,Wang YG,Mohammadi M,Schultz JEJ

    更新日期:2017-11-01 00:00:00

  • Identification and immunolocalisation of annexins V and VI, the major cardiac annexins, in rat heart.

    abstract:OBJECTIVE:The heart contains proteins of the annexin family, a unique group of calcium binding proteins. This study was aimed at identifying the major cardiac annexins and determining their distribution in the rat heart. METHODS:Annexins were isolated by affinity chromatography and purified by ion exchange high pressu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.7.1359

    authors: Doubell AF,Lazure C,Charbonneau C,Thibault G

    更新日期:1993-07-01 00:00:00

  • Effects of nitric oxide synthase inhibition on myocardial capillary permeability and reactive hyperaemic response.

    abstract:OBJECTIVE:The aim was to examine the role of nitric oxide (NO) in the myocardial microcirculation. METHODS:Open chest anaesthetised dogs received intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA; 0.5 mg.kg-1 over 30 min). Myocardial microvascular extraction fraction of a small hydrophilic solute (technetium ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Hansen PR,Haunsø S

    更新日期:1995-06-01 00:00:00

  • Marine n-3 PUFAs modulate IKs gating, channel expression, and location in membrane microdomains.

    abstract:AIMS:Polyunsaturated fatty n-3 acids (PUFAs) have been reported to exhibit antiarrhythmic properties. However, the mechanisms of action remain unclear. We studied the electrophysiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on IKs, and on the expression and location of Kv7.1 and KCNE1....

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvu250

    authors: Moreno C,de la Cruz A,Oliveras A,Kharche SR,Guizy M,Comes N,Starý T,Ronchi C,Rocchetti M,Baró I,Loussouarn G,Zaza A,Severi S,Felipe A,Valenzuela C

    更新日期:2015-02-01 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

  • Haemodynamic effects of arterial compliance, total peripheral resistance, and glyceryl trinitrate on regurgitant volume in aortic regurgitation.

    abstract:STUDY OBJECTIVE:Afterload reduction is known to reduce regurgitant flow in patients with aortic regurgitation. Both arterial compliance and total peripheral resistance are determinants of afterload. The aim of this study was to evaluate the influence of arterial compliance and total peripheral resistance on the regurgi...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/25.10.869

    authors: Slørdahl SA,Piene H

    更新日期:1991-10-01 00:00:00

  • A spectrum of functional effects for disease causing mutations in the Jervell and Lange-Nielsen syndrome.

    abstract:OBJECTIVE:Jervell and Lange-Nielsen syndrome (JLNS) is a recessively inherited long QT syndrome (LQTS) characterised by profound sensorineural deafness and predisposition to syncope and sudden cardiac death. Mutation analysis has established the presence of mutations in affected individuals in the genes KCNQ1 and KCNE1...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(01)00350-9

    authors: Huang L,Bitner-Glindzicz M,Tranebjaerg L,Tinker A

    更新日期:2001-09-01 00:00:00