Abstract:
Aims:MicroRNAs (miRNAs) have been implicated in the pathogenesis of pulmonary hypertension (PH), a multifactorial and progressive condition associated with an increased afterload of the right ventricle leading to heart failure and death. The main aim of this study was to correlate the levels of miR-424(322) with the severity and prognosis of PH and with right ventricle hypertrophy progression. Additionally, we intended to evaluate the mechanisms and signalling pathways whereby miR-424(322) secreted by pulmonary arterial endothelial cells (PAECs) impacts cardiomyocytes. Methods and results:Using quantitative real-time PCR, we showed that the levels of circulating miR-424(322) are higher in PH patients when compared with healthy subjects. Moreover, we found that miR-424(322) levels correlated with more severe symptoms and haemodynamics. In the subgroup of Eisenmenger syndrome patients, miR-424(322) displayed independent prognostic value. Furthermore, we demonstrated that miR-424(322) targets SMURF1, through which it sustains bone morphogenetic protein receptor 2 signalling. Moreover, we showed that hypoxia induces the secretion of miR-424(322) by PAECs, which after being taken up by cardiomyocytes leads to down-regulation of SMURF1. In the monocrotaline rat model of PH, we found an association between circulating miR-424(322) levels and the stage of right ventricle hypertrophy, as well as an inverse correlation between miR-424(322) and SMURF1 levels in the hypertrophied right ventricle. Conclusions:This study shows that miR-424(322) has diagnostic and prognostic value in PH patients, correlating with markers of disease severity. Additionally, miR-424(322) can target proteins with a direct effect on heart function, suggesting that this miRNA can act as a messenger linking pulmonary vascular disease and right ventricle hypertrophy.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Baptista R,Marques C,Catarino S,Enguita FJ,Costa MC,Matafome P,Zuzarte M,Castro G,Reis A,Monteiro P,Pêgo M,Pereira P,Girão Hdoi
10.1093/cvr/cvx187subject
Has Abstractpub_date
2018-01-01 00:00:00pages
53-64issue
1eissn
0008-6363issn
1755-3245pii
4139792journal_volume
114pub_type
杂志文章,多中心研究abstract::Extracellular potassium activity before and after coronary occlusion was measured in the canine heart by means of potassium-selective surface electrodes. In the ischaemic myocardium potassium activity rapidly increased from a preocclusion value of 3.2 +/- 0.3 mmol.litre-1 to 10 +/- 0.6 mmol.litre-1 within the first 5 ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/13.5.297
更新日期:1979-05-01 00:00:00
abstract:STUDY OBJECTIVE:It has been suggested that oxygenation of the isolated, crystalloid perfused, Langendorff rabbit heart is inadequate and that consequent hypoxia limits mechanical performance. The isolated working rabbit heart, which has a higher oxygen requirement than the Langendorff preparation, was used to investiga...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.3.198
更新日期:1991-03-01 00:00:00
abstract::Atrial fibrillation is the most common cardiac arrhythmia with an overall prevalence of almost 1%. Increasing prevalence and associated risks such as stroke and mortality have increased the need for better and more reliable therapeutic treatment. This has stimulated research to elucidate the pathophysiological mechani...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00367-4
更新日期:2001-10-01 00:00:00
abstract:OBJECTIVE:To investigate the physiological role of cAMP-dependent protein kinase A (PKA)-mediated, cardiac myosin binding protein C (MyBP-C) phosphorylation. METHODS:A cardiac MyBP-C cDNA lacking nine amino acids, which contained a phosphorylation site, was made, and subsequently used to generate multiple lines of tra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00273-5
更新日期:2001-07-01 00:00:00
abstract::Eighty-one consecutive patients representing a wide clinical spectrum were studied to assess the degree of limitation of the atrial extrastimulus technique for measurement of atrioventricular node refractoriness; and, to determine the relationship between conductivity and functional refractoriness of the atrioventricu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.8.457
更新日期:1982-08-01 00:00:00
abstract:OBJECTIVES:We measured the uptake of technetium-99m tetrofosmin (99m Tc) and thallium-201 (201 TI) in areas of healed transmural myocardial infarction and in the regions of acute peri-infarction ischemia. METHODS:Anesthetised pigs with a 1-month old transmural infarction elicited by permanent ligature of the left ante...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00316-7
更新日期:1998-04-01 00:00:00
abstract:OBJECTIVE:Macrophage migration inhibitory factor (MIF), which plays a pivotal role in the control of inflammatory responses, was first characterized as a T-cell cytokine, but later was also found as a pituitary peptide released in response to infection and stress. However, MIF's role and expression in the myocardium ha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00408-4
更新日期:2001-12-01 00:00:00
abstract::The theoretical possibilities and the practical limitations of the Xenon-133 (133Xe) method for the study of regional myocardial perfusion in man are discussed. The techniques for data acqusition and processing developed over the past 5 years are described in detail. Illustrative examples of experimental findings are ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.4.277
更新日期:1977-07-01 00:00:00
abstract:OBJECTIVE:3-Methylcholanthrene (MC), a polycylic aromatic hydrocarbon, induces atherogenesis in mice fed an atherogenic diet. In this study, we tested the hypothesis that MC would induce DNA adducts in mouse aortic smooth muscle cells (SMCs) and that cytochrome P4501B1 (CYP1B1) plays an important role in the activation...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00536-3
更新日期:2002-03-01 00:00:00
abstract::The interest in mouse electrophysiology is expanding fast, despite the marked differences between mouse and man. Different methods have become available to analyse the electrical activity in the mouse heart in vivo. The mouse genome can be altered with relative ease, which allows the molecular dissection of the variou...
journal_title:Cardiovascular research
pub_type: 评论,杂志文章,评审
doi:10.1016/s0008-6363(99)00335-1
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVES:Anthracyclines cause apoptotic death in many cell types through activation of the ceramide pathway. We tested the hypothesis that doxorubicin induces cardiac myocyte apoptosis through ceramide generation. METHODS:Adult rat ventricular myocytes were grown in the presence of 10% fetal calf serum, and exposed ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00142-x
更新日期:1999-08-01 00:00:00
abstract::The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.8.655
更新日期:1989-08-01 00:00:00
abstract:AIMS:Expression of extracellular matrix protein CCN1 is induced in end-stage ischaemic cardiomyopathy in humans, and after cardiac ischaemia and reperfusion in experimental animal models. Despite its well-documented angiogenic activities, CCN1 increases the cytotoxicities of the tumour necrosis factor family cytokines,...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt001
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVE:Stretch-activated cation channels (SAC) have been suggested to act as endothelial mechanosensors for hemodynamic forces. Ca(2+) influx through SAC could induce an intracellular Ca(2+) signal stimulating Ca(2+)-dependent synthesis of vasodilators like NO, prostacyclin, or EDHF. In the present study we tested w...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00476-x
更新日期:2002-01-01 00:00:00
abstract::Many observational studies and experimental and animal studies have demonstrated that estrogen therapy (ET) or hormone therapy (HT) significantly reduces the risk of coronary heart disease. Nonetheless, recent randomized controlled trials and the Nurses' Health Study in secondary prevention demonstrate trends toward a...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2005.12.004
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:Nitric oxide (NO) has been shown to induce apoptosis in cardiomyocytes under normoxic conditions. The ability of NO to induce apoptosis after ischemia-reperfusion, a situation of increased NO release in vivo, has not been investigated. The present study was undertaken to characterize the pathway of induction ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00272-2
更新日期:2000-02-01 00:00:00
abstract::Cardiomyocytes express a surprisingly large number of potassium channel types. The primary physiological functions of the currents conducted by these channels are to maintain the resting membrane potential and mediate action potential repolarization under basal conditions and in response to changes in the concentratio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa068
更新日期:2020-07-15 00:00:00
abstract:OBJECTIVE:Hereditary long QT syndrome (LQTS) is a genetically heterogeneous disease characterized by prolonged QT intervals and an increased risk for ventricular arrhythmias and sudden cardiac death. Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of LQTS. KCNQ1 is associated ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.003
更新日期:2005-08-15 00:00:00
abstract:AIMS:Insulin (Ins) resistance (IRES) associates to increased cardiovascular risk as observed in metabolic syndrome. Chronic stimulation of beta-adrenergic receptors (betaAR) due to exaggerated sympathetic nervous system activity is involved in the pathogenesis of IRES. The cellular levels of G protein coupled receptor ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp252
更新日期:2009-12-01 00:00:00
abstract:OBJECTIVE:Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. The pathway mediating endothelial cell apoptosis has not been fully established. Here we investigated the participation of peroxisome proliferat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.06.032
更新日期:2007-11-01 00:00:00
abstract:AIMS:Free fatty acids induce apoptosis in cardiomyocytes, which is implicated in lipotoxic cardiomyopathy. However, the underlying mechanisms remain not fully understood. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr145
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVES:Action potential prolongation related to the alteration of several membrane currents is constantly reported in heart failure (HF) but reports about its role in arrhythmogenesis are sparse. Our aim was to determine, by analogy with long QT syndromes, whether prolonged repolarization is associated with increas...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00236-5
更新日期:2002-04-01 00:00:00
abstract:OBJECTIVE:While natriuretic peptides can inhibit growth of vascular muscle cells (VSMC), controversy exists as to whether this effect is mediated via the guanylate cyclase-coupled receptors, NPR-A and NPR-B, or the clearance receptor, NPR-C. The original aim of this study was to examine the mechanism by which the NPR-C...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00086-2
更新日期:1997-07-01 00:00:00
abstract:AIMS:A problem in generating artificial tissues is supplying nutrients to cells within 3D constructs. The use of a decellularized biological vascularized matrix with preserved pedicles (BioVaM), as a scaffold, appears to aid the generation of perfusable tissue constructs in vitro. To prevent vessel occlusion upon impla...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp370
更新日期:2010-03-01 00:00:00
abstract:AIMS:Elderly patients with heart failure with reduced ejection fraction (HFrEF) have worse prognosis and less often receive guideline-recommended therapies. We aim to better understand the underlying pathophysiological processes associated with aging in HFrEF potentially leading to targeted therapies in this vulnerable...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa279
更新日期:2020-10-01 00:00:00
abstract:OBJECTIVE:The aim was to study (1) the effects of intracoronary saralasin, an angiotensin II receptor antagonist, on ischaemia induced and reperfusion induced regional cardiac noradrenaline release and ventricular arrhythmias; and (2) the implication of angiotensin II in coronary constriction during myocardial ischaemi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.10.968
更新日期:1992-10-01 00:00:00
abstract:AIMS:17β-Oestradiol (E2) and its receptors (ERα and ERβ) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not ful...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs281
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVE:We determine if action potential duration (APD) shortening and cardioprotection are separable phenomena in ATP-sensitive potassium channel (KATP) openers which protect ischemic myocardium via a glyburide-reversible mechanism. METHODS:We determined the effect of the weakly vasodilating KATP opener, BMS-180448...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 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:AIMS:Ischaemic preconditioning (IPC) protects the heart against prolonged lethal ischaemia through a signalling cascade involving Akt, glycogen synthase kinase-3β (GSK-3β), and mitochondrial ATP-sensitive potassium channels (mitoK(ATP)). We previously demonstrated the involvement of the Wnt pathway in IPC in vivo via G...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr002
更新日期:2011-04-01 00:00:00