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 Resjournal_title
Cardiovascular researchauthors
Merino D,Villar AV,García R,Tramullas M,Ruiz L,Ribas C,Cabezudo S,Nistal JF,Hurlé MAdoi
10.1093/cvr/cvw076subject
Has Abstractpub_date
2016-06-01 00:00:00pages
331-45issue
3eissn
0008-6363issn
1755-3245pii
cvw076journal_volume
110pub_type
杂志文章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
更新日期:1988-05-01 00:00:00
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
更新日期:1985-05-01 00:00:00
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
更新日期:1980-05-01 00:00:00
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
更新日期:2020-07-16 00:00:00
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
更新日期:1988-06-01 00:00:00
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:
更新日期:1995-01-01 00:00:00
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
更新日期:1984-11-01 00:00:00
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
更新日期:1996-11-01 00:00:00
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
更新日期:1997-04-01 00:00:00
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
更新日期:1991-07-01 00:00:00
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
更新日期:2020-03-01 00:00:00
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
更新日期:2005-08-15 00:00:00
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
更新日期:1999-02-01 00:00:00
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
更新日期:2003-08-01 00:00:00
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
更新日期:1999-12-01 00:00:00
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
更新日期:2008-04-01 00:00:00
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
更新日期:2015-03-01 00:00:00
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
更新日期:2013-03-01 00:00:00
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
更新日期:2001-03-01 00:00:00
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
更新日期:1985-09-01 00:00:00
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
更新日期:2008-09-01 00:00:00
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
更新日期:1999-05-01 00:00:00
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
更新日期:1979-09-01 00:00:00
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
更新日期:2017-11-01 00:00:00
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
更新日期:1993-07-01 00:00:00
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:
更新日期:1995-06-01 00:00:00
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
更新日期:2015-02-01 00:00:00
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
更新日期:2000-07-01 00:00:00
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
更新日期:1991-10-01 00:00:00
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
更新日期:2001-09-01 00:00:00