Abstract:
Aims:We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results:The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P < 0.001; left ventricular end diastolic volume: -4%, P = 0.002), and increased LVEF (+14%, P < 0.0001) relative to baseline values. Gene profiling revealed that EV-treated hearts were enriched for tissue reparative pathways. Conclusion:Extracellular vesicles secreted by iPSC-Pg are effective in the treatment of CHF, possibly, in part, through their specific miRNA signature and the associated stimulation of distinct cardioprotective pathways. The processing and regulatory advantages of EV could make them effective substitutes for cell transplantation.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
El Harane N,Kervadec A,Bellamy V,Pidial L,Neametalla HJ,Perier MC,Lima Correa B,Thiébault L,Cagnard N,Duché A,Brunaud C,Lemitre M,Gauthier J,Bourdillon AT,Renault MP,Hovhannisyan Y,Paiva S,Colas AR,Agbulut O,Hagègedoi
10.1093/eurheartj/ehy012subject
Has Abstractpub_date
2018-05-21 00:00:00pages
1835-1847issue
20eissn
0195-668Xissn
1522-9645pii
4840711journal_volume
39pub_type
杂志文章abstract::Organic nitrates exert their effect by direct inhibition of vascular tone, resulting in decreased myocardial oxygen demand and improved oxygen supply. Less well known is the effect of nitrates on blood rheology. To evaluate the haemodiluting effect of intravenous nitroglycerin we studied 70 consecutive patients admitt...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060362
更新日期:1994-01-01 00:00:00
abstract:AIMS:To investigate the efficacy and safety of a cardiac resynchronization therapy with cardioverter-defibrillator (CRT-D) device with simplified ventricular tachycardia management in patients with non-ischaemic heart failure (HF) and primary prevention implantable cardioverter defibrillator (ICD) indication. METHODS ...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究
doi:10.1093/eurheartj/ehp247
更新日期:2009-11-01 00:00:00
abstract:AIMS:Dysregulation of the bone morphogenetic protein receptor type 2 (BMPR2) is a hallmark feature that has been described in several forms of pulmonary hypertension. We recently identified the microRNA miR-20a within a highly conserved pathway as a regulator of the expression of BMPR2. To address the pathophysiologica...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehs060
更新日期:2014-12-01 00:00:00
abstract:AIMS:Clonal haematopoiesis of indeterminate potential (CHIP), defined as the presence of an expanded somatic blood cell clone without other haematological abnormalities, was recently shown to increase with age and is associated with coronary artery disease and calcification. The most commonly mutated CHIP genes, DNMT3A...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehz591
更新日期:2020-02-21 00:00:00
abstract:Aims:Naturally secreted nanovesicles known as exosomes are required for the regenerative effects of cardiosphere-derived cells (CDCs), and exosomes mimic the benefits of CDCs in rodents. Nevertheless, exosomes have not been studied in a translationally realistic large-animal model. We sought to optimize delivery and as...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehw240
更新日期:2017-01-14 00:00:00
abstract:AIMS:Recent randomized trials suggest that intensive glycaemic control fails to reduce heart failure-related events in patients with diabetes. The molecular cues underlying persistent myocardial damage despite normoglycaemia restoration remain elusive. MicroRNAs (miRNAs), a class of small non-coding RNAs, orchestrate t...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehv599
更新日期:2016-02-07 00:00:00
abstract:AIMS:We aimed to assess the contemporary outcome of Eisenmenger syndrome (ES), delineate the use of disease targeting therapies (DTT) in these patients and to investigate the effect of treatment on outcome in the community. METHODS AND RESULTS:Patients with ES were systematically identified from the German National Re...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehv743
更新日期:2016-05-07 00:00:00
abstract::Aims To assess whether coronary flow velocity reserve following stent implantation is predictive of the subsequent need of target lesion revascularization. Methods and Results The outcome was examined of 417 patients enrolled in a multicentre prospective randomized study (DESTINI), who received a successful single ves...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1053/euhj.2001.2734
更新日期:2002-02-01 00:00:00
abstract:AIMS:We investigated the role of asymmetric dimethylarginine (ADMA) for clinical outcome of patients with unstable angina. METHODS AND RESULTS:Forty-five patients with stable angina, 36 patients with unstable angina, and 40 healthy controls were included in this study. Coronary artery disease (CAD) patients were prosp...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehi287
更新日期:2005-09-01 00:00:00
abstract:AIMS:Induced pluripotent stem cells (iPSCs) provide a unique opportunity for the generation of patient-specific cells for use in disease modelling, drug screening, and regenerative medicine. The aim of this study was to compare human-induced pluripotent stem cells (hiPSCs) derived from different somatic cell sources re...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehs203
更新日期:2013-09-01 00:00:00
abstract:AIMS:To evaluate the prevalence, clinical significance, and prognosis of latent Brugada syndrome (BrS) in patients with new-onset atrial fibrillation (AF) unmasked by class 1C antiarrhythmic drugs. METHODS AND RESULTS:Between January 2000 and June 2008, all consecutive patients with new-onset AF, who after flecainide ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehp326
更新日期:2009-12-01 00:00:00
abstract::Atrial fibrillation is a frequent cause of stroke; in the elderly, more than 20% of strokes are attributed to this common arrhythmia. Anticoagulation with warfarin reduces the risk of stroke by ∼60%; however, a large proportion of patients with atrial fibrillation do not receive this treatment because of relative/abso...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehr393
更新日期:2012-03-01 00:00:00
abstract:AIM:Ventricular fibrosis is promoted by many effectors that chronically activate phospholipase D (PLD), and induces cardiac dysfunction and heart failure in cardiovascular diseases. Since ethanolamine is a product of PLD, we hypothesised that an administration of an analogue of ethanolamine, N-methylethanolamine (MEA),...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1016/j.ehj.2004.05.003
更新日期:2004-07-01 00:00:00
abstract::Re-entry was demonstrated as a self-perpetuating mechanism as early as 1906. It may lead to single-cycle electrocardiographic phenomena as well as reciprocating tachycardias. Factors favouring re-entry are as follows. Unidirectional or temporary local block of conduction, a mechanism always involved in initiation of r...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/5.suppl_b.19
更新日期:1984-09-01 00:00:00
abstract::Exercise-induced U-wave inversion on chest wall mapping was compared with coronary arteriographic findings in 160 consecutive patients who presented with chest pain suggestive of ischaemic heart disease. ECG recordings were made from 16 points on the chest wall before, during and after exercise. None of the 27 patient...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a061883
更新日期:1985-05-01 00:00:00
abstract:AIMS:Despite disparities in pathophysiology and disease manifestation between male and female patients with heart failure, studies focusing on sex differences in biomarkers are scarce. The purpose of this study was to assess sex-specific variation in clinical characteristics and biomarker levels to gain more understand...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/eht152
更新日期:2013-08-01 00:00:00
abstract::Clinical reports show that electrical stimulation of the spinal cord reduces symptoms of angina pectoris, but so far have not provided evidence on the mechanisms involved. The hypothesis for this study was that inhibition of spinothalamic tract transmission may account for this result. Extracellular potentials of 28 s...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/14.1.96
更新日期:1993-01-01 00:00:00
abstract:AIMS:In the dual antiplatelet therapy (DAPT) study, continued thienopyridine beyond 12 months after drug-eluting stent placement was associated with increased mortality compared with placebo. We sought to evaluate factors related to mortality in randomized patients receiving either drug-eluting or bare metal stents in ...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/ehv614
更新日期:2016-01-21 00:00:00
abstract::Coronary arteries of anomalous origin with subsequent coursing between the aorta and pulmonary trunk can cause ischaemia, infarction or sudden death. However, reports of surgical correction are sparse due to the rarity of ante-mortem diagnosis. We report two cases in which symptoms were related to anomalous origin of ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/12.7.832
更新日期:1991-07-01 00:00:00
abstract:AIMS:we investigated the relationship between sublingual perfused capillary density (PCD) as a measure of tissue perfusion and outcome (i.e. occurrence of organ failure and mortality) in patients with cardiogenic shock from acute myocardial infarction. METHODS AND RESULTS:we performed a prospective study in 68 patient...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehq324
更新日期:2010-12-01 00:00:00
abstract:AIMS:This study assessed the relationship between inflammatory mediators and indices of infarct size and left-ventricular (LV) remodelling following successful primary percutaneous coronary intervention (PCI) in patients with first time ST elevation myocardial infarction (MI). METHODS AND RESULTS:Forty-two patients ad...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehp070
更新日期:2009-05-01 00:00:00
abstract::Morphological changes in human myocardium associated with pressure overload-induced left ventricular hypertrophy were studied in 22 normal and 21 hypertrophic hearts obtained at autopsy. Samples were obtained from the left lateral ventricular wall, half way between the apex and the base. Myocyte dimensions, polyploidi...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a059928
更新日期:1991-04-01 00:00:00
abstract::Transient ischaemic episodes, defined as chest pain with ST segment elevation resolving in less than 15 min, have been encountered in 18 out of 130 patients during or in the 12h following percutaneous transluminal angioplasty (PTCA). During PTCA, ischaemic episodes occurred in 11 patients (8.5%) along with complete co...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a061669
更新日期:1984-05-01 00:00:00
abstract::Cardiac troponins (cTns) I and T have long been the most successful cardiac-specific circulating biomarkers in cardiovascular (CV) medicine, having changed dramatically the diagnosis of acute myocardial infarction, while being independent predictors of outcome in several cardiac conditions and non-cardiac conditions. ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehaa083
更新日期:2020-11-01 00:00:00
abstract::Thrombolytic treatment efficacy is greater when the delay between onset of pain and treatment is short. One way to shorten this delay is to give treatment at home, but one cannot recommend this technique if it has not been demonstrated first, that pre-hospital thrombolysis is feasible and safe, and second, that it is ...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/11.suppl_f.43
更新日期:1990-08-01 00:00:00
abstract::Atrial fibrillation is a common arrhythmia and one which may cause pilot incapacitation. In many cases there may be no more than one episode and there will be no organic heart disease. Prediction of the risk of recurrence is not possible. Atrial fibrillation in both paroxysmal and persistent forms should be disqualify...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/5.suppl_a.89
更新日期:1984-03-01 00:00:00
abstract::To compare the blood pressure (BP) changes during a long-distance run with those during bicycle ergometry, nine normotensive and 18 hypertensive joggers were studied by means of ambulatory intra-arterial monitoring. In all subjects the ergometric test caused a progressive increase in systolic and little change in dias...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a059709
更新日期:1990-04-01 00:00:00
abstract:Aims:To analyse reasons, timing and predictors of hospital readmissions after transcatheter aortic valve implantation (TAVI). Methods and results:Patients included in the Bern TAVI Registry between August 2007 and June 2014 were analysed. Fine and Gray competing risk regression was used to identify factors predictive ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehx182
更新日期:2017-07-21 00:00:00
abstract::To determine if dobutamine-induced myocardial ischaemia causes abnormalities in Doppler parameters of left ventricular ejection and filling and to assess early effects of successful coronary angioplasty (PTCA) on these parameters, dobutamine stress echocardiography and Doppler studies were performed once in 11 normal ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/14.8.1011
更新日期:1993-08-01 00:00:00
abstract::One of the main areas of interest in interventional cardiology is the understanding, and ultimate prevention of restenosis after an initially successful percutaneous transluminal coronary angioplasty. Restenosis is the recurrence of luminal narrowing following angioplasty, and still frustrates the late results in the ...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验,评审
doi:10.1093/eurheartj/16.suppl_l.56
更新日期:1995-11-01 00:00:00