Abstract:
AIMS:Pulmonary hypertension (PH) is a devastating condition for which no disease-modifying therapies exist. PH is recognized as proliferative disease of the pulmonary artery (PA). In the experimental newborn calf model of hypoxia-induced PH, adventitial fibroblasts in the PA wall exhibit a heightened replication index. Because elevated platelet-derived growth factor β receptor (PDGFβ-R) signalling is associated with PH, we tested the hypothesis that the activation of PDGFβ-R contributes to fibroblast proliferation and adventitial remodelling in PH. METHODS AND RESULTS:Newborn calves were exposed to either ambient air (P(B) = 640 mmHg) (Neo-C) or high altitude (P(B) = 445 mm Hg) (Neo-PH) for 2 weeks. PDGFβ-R phosphorylation was markedly elevated in PA adventitia of Neo-PH calves as well as in cultured PA fibroblasts isolated from Neo-PH animals. PDGFβ-R activation with PDGF-BB stimulated higher replication in Neo-PH cells compared with that of control fibroblasts. PDGF-BB-induced proliferation was dependent on reactive oxygen species generation and extracellular signal-regulated kinase1/2 activation in both cell populations; however, only Neo-PH cell division via PDGFβ-R activation displayed a unique dependence on c-Jun N-terminal kinase1 (JNK1) stimulation as the blockade of JNK1 with SP600125, a pharmacological antagonist of the JNK pathway, and JNK1-targeted siRNA selectively blunted Neo-PH cell proliferation. CONCLUSIONS:Our data strongly suggest that hypoxia-induced modified cells engage the PDGFβ-R-JNK1 axis to confer distinctively heightened proliferation and adventitial remodelling in PH.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Panzhinskiy E,Zawada WM,Stenmark KR,Das Mdoi
10.1093/cvr/cvs194subject
Has Abstractpub_date
2012-08-01 00:00:00pages
356-65issue
3eissn
0008-6363issn
1755-3245pii
cvs194journal_volume
95pub_type
杂志文章abstract:AIMS:Atrial fibrillation (AF) is the most common cardiac arrhythmia, and early-onset lone AF has been linked to mutations in genes encoding ion channels. Mutations in the pore forming subunit KV4.3 leading to an increase in the transient outward potassium current (Ito) have previously been associated with the Brugada S...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt028
更新日期:2013-06-01 00:00:00
abstract::Nitric oxide (NO) is a highly reactive, free radical signalling molecule that is constitutively released in cardiomyocytes by both the endothelial and neuronal isoforms of nitric oxide synthase (eNOS and nNOS, respectively). There are increasing data indicating that NO modulates various proteins involved in excitation...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvm012
更新日期:2008-01-15 00:00:00
abstract:OBJECTIVE:The aim was to assess the significance of polymorphonuclear leucocytes on the myocardial capillary permeability to a small hydrophilic indicator, on the vascular tone of the resistance vessels, and on contractile function following ischaemia and reperfusion. METHODS:Open chest, anaesthetised dogs were random...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.7.1288
更新日期:1993-07-01 00:00:00
abstract:AIMS:The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. METHODS AND RESULTS:PRR was expressed in human mammary arteries and in cultur...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs204
更新日期:2012-08-01 00:00:00
abstract::A mathematical formulation of the blood flow behaviour through a capillaron model is described. The formulation is applied to the analysis of post-occlusion (reactive) hyperaemia and autoregulation. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.1.13
更新日期:1976-01-01 00:00:00
abstract:OBJECTIVES:Plasma endothelin (ET) concentrations are increased in heart failure. The aims of the present study were to investigate to what extent cardiac ET mRNA expression is induced in ischemic heart failure and whether there may be compensatory downregulation of myocardial mRNA levels for the ETA and ETB receptor su...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00266-0
更新日期:1997-03-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to determine if the adaptational process of the cardiac calcium channel to pressure overload observed in rat heart also occurs in species characterised by a higher sensitivity to external calcium than in the rat. This adaptation occurs via a maintained density of dihydropyridine receptors an...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.10.875
更新日期:1991-10-01 00:00:00
abstract:AIMS:Baicalin is the major component found in Scutellaria baicalensis root, a widely used herb in traditional Chinese medicine. Although it has been used for thousands of years to treat stroke, the mechanisms of action of S. baicalensis have not been clearly elucidated. In this report, we studied the modulation of angi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq296
更新日期:2011-02-01 00:00:00
abstract::The afterload dependency of relaxation rate was reappraised in isolated canine hearts both in isovolumic and isobaric contractions by using the reliable exponential method in which the asymptote LV pressure (P chi) is variable. This method provided a closer correlation (r = 0.999 +/- 0.001) between the measured LV pre...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.10.649
更新日期:1985-10-01 00:00:00
abstract:AIMS:Adequate microcirculatory perfusion, and not just opening of occluded arteries, is critical to salvage heart tissue following myocardial infarction. However, the degree of microvascular perfusion taking place is not known, limited primarily by an inability to directly image coronary microcirculation in a beating h...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz118
更新日期:2019-11-01 00:00:00
abstract:AIMS:G-protein-coupled receptors (GPCRs) modulate vascular tone, at least in part, via matrix metalloproteinase (MMP) transactivation of the epidermal growth factor receptor (EGFR). We previously have identified novel signalling pathways downstream of the EGFR suggestive of mitogen-activated protein kinase and mitochon...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp230
更新日期:2009-12-01 00:00:00
abstract:OBJECTIVE:Recently, we have found that rat CMV (RCMV) infected smooth muscle cells (SMCs) in rat carotid arteries when administered 14 days after balloon injury. In the present study we investigated (1) the long term effects of CMV infection on neointimal cross-sectional area, and (2) whether the phenotype of the intim...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00189-2
更新日期:1997-11-01 00:00:00
abstract:OBJECTIVES:This study examined the effects of diet-induced hypercholesterolemia on the extent of postischemic myocyte apoptosis and elucidated the potential mechanisms involved. Furthermore, the effects of rosiglitazone (RSG) on postischemic myocardial apoptosis in HC rabbits were investigated. METHODS:Male New Zealan...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.12.027
更新日期:2004-04-01 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:OBJECTIVE:Insulin seems to have vasodilator properties, but it is unclear if insulin in postprandial concentrations is a specific vasodilator of skeletal muscle resistance arterioles only or that various types of vessels are affected. The aim of the present study was to determine the direct effects and the time course ...
journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
doi:10.1016/s0008-6363(97)00035-7
更新日期:1997-04-01 00:00:00
abstract:OBJECTIVE:Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), acts on the pituitary and the hypothalamus to stimulate the release of growth hormone (GH) and promotes appetite and adiposity. It has also been reported to increase myocardial contractility, induce vasodilation, and protect again...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.01.024
更新日期:2004-06-01 00:00:00
abstract:AIMS:Intracellular Ca(2+) ([Ca(2+)](i)) regulation in endothelial cells depends on transient receptor potential channels (TRPs), and the role of canonical TRPs (TRPCs) during hypoxia-reoxygenation (H-R) is unclear. We hypothesized that TRPC3 contributes to endothelial nitric oxide (NO) release and that H-R may reduce T...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr102
更新日期:2011-08-01 00:00:00
abstract:OBJECTIVE:We investigated the efficacy of nicaraven in reducing myocardial as well as coronary endothelial preservation-reperfusion (P/R) injury. METHODS:In experiment I, isolated rat hearts were mounted on a Langendorff (L) apparatus to estimate the baseline cardiac function. Group 1, 8- and 12-h storage in histidine...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00268-4
更新日期:1997-03-01 00:00:00
abstract::Conventional antithrombotic treatments with antiplatelet, anticoagulant or fibrinolytic drugs are not uniformly successful and are associated with hemorrhagic side effects. Thus, new approaches to the prevention and treatment of arterial thrombosis are desirable. The gene transfer approach is particularly attractive b...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00153-3
更新日期:1997-09-01 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:Myogenic tone, which has a major role in the regulation of local blood flow, refers to the ability of vascular smooth muscle to adapt its contractility to changes in transmural pressure. Although Rho-kinase is involved in myogenic tone, the pathway involved remains unclear, especially concerning translocation...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.10.020
更新日期:2007-01-01 00:00:00
abstract::Ultrasound has become a useful high resolution imaging modality for examining the cardiac microcirculation. With the use of microbubbles as an ultrasound contrast agent, ultrasound can be utilized to image the microcirculation and detect capillary flow abnormalities in acute ischaemia. A wide range of ultrasound frequ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp206
更新日期:2009-09-01 00:00:00
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
更新日期:2000-01-14 00:00:00
abstract:STUDY OBJECTIVE:The aim was to investigate whether basal coronary vascular tone and myocardial perfusion depend upon endothelial nitric oxide (NO) synthesis. DESIGN:Myocardial blood flow and vascular resistance of the left and right ventricles were studied before and after intravenous infusions of either NG-nitro-L-ar...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.8.700
更新日期:1991-08-01 00:00:00
abstract:AIMS:Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that contributes to pathogenic cardiac remodelling via mechanisms that involve oxidative stress. However, the direct impact of TGF-beta1 on contractile function of ventricular myocytes is incompletely understood. METHODS AND RESULTS:Reacti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm022
更新日期:2008-01-01 00:00:00
abstract::The voltage- and rate-dependence of the depression of the maximum rate of depolarisation (Vmax) by therapeutic concentrations of flecainide and lorcainide were studied in guinea-pig ventricle by standard microelectrode techniques. At normal resting potentials the drugs produced only minor depression of Vmax in the abs...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.5.251
更新日期:1983-05-01 00:00:00
abstract::The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasingly apparent is tha...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvn054
更新日期:2008-07-15 00:00:00
abstract::The development of the heart is a complex process during which different cell types progressively contribute to shape a four-chambered pumping organ. Over the last decades, our understanding of the specification and transcriptional regulation of cardiac development has been greatly augmented as has our understanding o...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvr078
更新日期:2011-07-15 00:00:00
abstract:OBJECTIVE:Matrix metalloproteinase-9 (MMP-9) activity is up regulated in the heart subjected to ischemic insult. Whether increased MMP-9 activity contributes to acute myocardial injury after ischemia-reperfusion remains unknown. To investigate the role of MMP-9 in myocardial infarction, we utilized a MMP-9 knockout mou...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00254-7
更新日期:2002-06-01 00:00:00
abstract:AIMS:Our previous studies demonstrated that inflammation contributes to atherosclerosis through disruption of the low density lipoprotein receptor (LDLr) pathway. However, this effect is overridden by rapamycin, which is an inhibitor of mammalian target of rapamycin (mTOR). This study investigated the role of the mTOR ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt203
更新日期:2013-12-01 00:00:00