Abstract:
AIMS:The proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also leads to structural and functional changes of the heart. METHODS AND RESULTS:Female domestic pigs were randomized to a normal diet without (N) or with twice-weekly subcutaneous injections of the proteasome inhibitor MLN-273 (0.08 mg/kg, N + PSI, n = 5 each group). In vivo data on cardiac structure and function as well as myocardial perfusion and microvascular permeability response to adenosine and dobutamine were obtained by electron beam computed tomography after 11 weeks. Subsequent ex vivo myocardial analyses included immunoblotting, immunostaining, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling), Masson trichrome, and Congo red staining. Compared with N, an increase in LV mass was observed in N + PSI (106.5 ± 16.4 g vs. 183.1 ± 24.2 g, P < 0.05). The early to late diastolic filling ratio was increased in N + PSI vs. N (3.5 ± 0.6 vs. 1.8 ± 0.1, P < 0.05). The EF tended to be lower (46 ± 12% and 53 ± 9%, respectively) and cardiac output was significantly lower in N + PSI than in N (2.9 ± 1.1 vs. 4.7 ± 1.1 L/min, P < 0.05). Tissue analyses demonstrated an accumulation of proteasome substrates, apoptosis, and fibrosis in the PSI group. Compared with N, the myocardial perfusion response was reduced and microvascular permeability was increased in N + PSI. CONCLUSION:The current study demonstrates that chronic proeasome inhibition affects the cardiovascular system, leading to functional and structural alteration of the heart consistent with a hypertrophic-restrictive cardiomyopathy phenotype.
journal_name
Eur J Heart Failjournal_title
European journal of heart failureauthors
Herrmann J,Wohlert C,Saguner AM,Flores A,Nesbitt LL,Chade A,Lerman LO,Lerman Adoi
10.1093/eurjhf/hft034subject
Has Abstractpub_date
2013-06-01 00:00:00pages
614-23issue
6eissn
1388-9842issn
1879-0844pii
hft034journal_volume
15pub_type
杂志文章abstract:AIMS:Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF. METHODS AND RESULTS:Multiple dat...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.1643
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVE:To determine the acute vasodilator effect of sublingual sildenafil in heart transplant candidates with severe pulmonary hypertension due to severe left ventricular dysfunction (LVD). BACKGROUND:Pulmonary hypertension confers an increased risk of early graft failure. PATIENTS AND METHODS:Seven patients, (mea...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/j.ejheart.2003.11.015
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND:Plasma renin activity is normal in left ventricular dysfunction in the absence of diuretic therapy. In health there is a reciprocal relationship between renin and atrial natriuretic peptide (ANP) but a positive correlation in advanced heart failure. The relationship between renin and ANP in mild left ventric...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/s1388-9842(99)00058-6
更新日期:1999-12-01 00:00:00
abstract:AIMS:As pulmonary arterial hypertension (PAH) is associated with significant morbidity and mortality, particularly among patients with right ventricular (RV) dysfunction, we aimed to determine the impact of therapy to reduce pulmonary vascular resistance (PVR) on RV and LV deformation in PAH. METHODS AND RESULTS:Right...
journal_title:European journal of heart failure
pub_type: 杂志文章,随机对照试验
doi:10.1002/ejhf.177
更新日期:2015-01-01 00:00:00
abstract:AIMS:Right ventricular (RV) dysfunction and pulmonary hypertension (PH) are increasingly recognized in heart failure with preserved ejection fraction (HFpEF). The prevalence and prognostic value of RV dysfunction in HFpEF have been widely but variably reported. We therefore conducted a systematic review and meta-analys...
journal_title:European journal of heart failure
pub_type: 杂志文章,meta分析,评审
doi:10.1002/ejhf.630
更新日期:2016-12-01 00:00:00
abstract:AIMS:Women with heart failure (HF) are under-represented in individual randomized clinical trials (RCTs). Little is known about sex-specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectr...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.1740
更新日期:2020-05-01 00:00:00
abstract:BACKGROUND:The association between serum digoxin concentration (SDC) and outcomes in women with heart failure (HF) has not been well studied. AIMS:To test the hypothesis that the effect of digoxin on outcomes in women with HF is bi-directional and dependent on SDC, as in men, and is modified by ejection fraction (EF)....
journal_title:European journal of heart failure
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ejheart.2005.10.002
更新日期:2006-06-01 00:00:00
abstract:AIMS:The identification of valuable markers of sudden cardiac death (SCD) in patients with established HF remains a challenge. We sought to assess the value of clinical, echocardiographic and biochemical variables to predict SCD in a consecutive cohort of patients with heart failure (HF) due to systolic dysfunction. M...
journal_title:European journal of heart failure
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ejheart.2007.05.001
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND AND AIMS:The diagnosis of heart failure is an important clinical problem and yet reported diagnostic accuracy in primary care is less than 50%. We established a Rapid Access Heart Failure Clinic (RAHFC) in a district general hospital serving a population of 292,000 in SE London, UK, to diagnose and manage ne...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/s1388-9842(00)00108-2
更新日期:2000-12-01 00:00:00
abstract::The published version of this paper contained an error. The part C of the figure only has the header "multiple organs", whereas it must read: “HF does not affect multiple organs”. ...
journal_title:European journal of heart failure
pub_type: 已发布勘误
doi:10.1002/ejhf.499
更新日期:2016-02-01 00:00:00
abstract:AIMS:To investigate the prognostic value of autonomic variables in patients with symptomatic chronic heart failure (HF) treated according to current recommendations. METHODS AND RESULTS:We analysed 24 h time-domain [standard deviation of all normal-to-normal RR intervals (SDNN)], frequency-domain [very low frequency a...
journal_title:European journal of heart failure
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/eurjhf/hfs126
更新日期:2012-12-01 00:00:00
abstract:AIMS:Acute heart failure (AHF) has a poor prognosis. We evaluated 3- and 12-month mortality in different clinical classes of AHF patients from 30 European countries who were included in the EuroHeart Failure Survey (EHFS) II. METHODS AND RESULTS:Follow-up data were available for 2981 AHF patients, of these 62% had a h...
journal_title:European journal of heart failure
pub_type: 杂志文章,多中心研究
doi:10.1093/eurjhf/hfq002
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND:Patients with chronic heart failure (CHF) have frequent episodes of exacerbation leading to recurrent hospitalization. AIMS:To explore factors related to patients seeking care for worsening CHF. METHODS:Eighty-eight patients diagnosed with a deteriorating CHF condition were interviewed. Data were analysed ...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/j.ejheart.2006.11.002
更新日期:2007-06-01 00:00:00
abstract:INTRODUCTION:Atrial fibrillation (AF) is common in patients with heart failure (HF) due to left ventricular systolic dysfunction (LVSD), with conflicting prognostic data. The aim of our study was to assess the prevalence and incidence of AF in patients with HF and to determine the prognostic impact of baseline AF and t...
journal_title:European journal of heart failure
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ejheart.2006.08.004
更新日期:2007-03-01 00:00:00
abstract:AIMS:We sought to test the utility of weight gain algorithms to predict episodes of worsening heart failure (WHF) using home-telemonitoring data collected as part of the TEN-HMS study. METHODS AND RESULTS:Simple rule-of-thumb (RoT) algorithms (i.e. 3 lbs in 1 day and 5 lbs in 3 days) and a moving average convergence d...
journal_title:European journal of heart failure
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/eurjhf/hfp033
更新日期:2009-04-01 00:00:00
abstract:AIMS:Heart failure (HF) quality registries report quality of care but it is unknown whether they improve outcomes. The aims were to assess predictors of enrolment in a HF registry, test the hypothesis that enrolment in a HF registry is associated with reduced mortality, and assess potential explanatory factors for this...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.762
更新日期:2017-09-01 00:00:00
abstract::Anti-beta-1-adrenergic receptor antibodies (anti-β1AR Abs) have long been implicated in the pathogenesis of dilated cardiomyopathy (DCM). It is believed that these autoantibodies bind to and constitutively stimulate the β1AR to promote pathological cardiac remodelling and β1AR desensitization and downregulation. The p...
journal_title:European journal of heart failure
pub_type: 杂志文章,评审
doi:10.1093/eurjhf/hft065
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Most patients suspected of having heart failure (HF) will get a 12-lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its management has rarely been investigated. METHODS:The EuroHeart Failure survey identified 11,327 patients hospitalised with a suspected diagnosis of HF from 115...
journal_title:European journal of heart failure
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ejheart.2006.11.003
更新日期:2007-05-01 00:00:00
abstract:AIM:Heart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RDT) might be helpful and there are no data currently in humans with HFpEF. METHODS AND RESULTS:In this single-centre, randomized, open-controlled s...
journal_title:European journal of heart failure
pub_type: 杂志文章,随机对照试验
doi:10.1002/ejhf.502
更新日期:2016-06-01 00:00:00
abstract:AIMS:The aim of this review is to assess the effects of exercise training on the symptoms of depression in heart failure (HF) patients. METHODS AND RESULTS:Randomized controlled trials of exercise training in patients with HF and symptoms of depression were identified. The depression data were pooled using meta-analys...
journal_title:European journal of heart failure
pub_type: 杂志文章,meta分析,评审
doi:10.1002/ejhf.101
更新日期:2014-07-01 00:00:00
abstract:AIMS:Heart failure (HF) patients with a mid-range ejection fraction (HFmrEF) are not well characterized. Accordingly, we examined the epidemiology, pathophysiology and clinical outcomes of HF patients with a left ventricular ejection fraction (LVEF) of 40-50%. METHODS AND RESULTS:We identified 168 patients with an LVE...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.879
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND:Oxygen (O2) uptake at peak exercise (VO2 peak) is an objective measurement of functional capacity in patients with chronic heart failure (CHF). The significance of recovery O2 kinetics parameters in predicting exercise capacity, and the parameters of submaximal exercise testing have not been thoroughly exami...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/s1388-9842(01)00187-8
更新日期:2001-12-01 00:00:00
abstract::Dilated cardiomyopathy (DCM) represents a particular aetiology of systolic heart failure that frequently has a genetic background and usually affects young patients with few co-morbidities. The prognosis of DCM has improved substantially during the last decades due to more accurate aetiological characterization, the r...
journal_title:European journal of heart failure
pub_type: 杂志文章,评审
doi:10.1002/ejhf.1103
更新日期:2018-02-01 00:00:00
abstract:AIMS:Endothelial dysfunction has been shown to correlate with severity of congestive heart failure (CHF) and recent data suggest morphological changes of peripheral vasculature to be associated with the syndrome. We therefore investigated the hypothesis that vascular remodeling is associated with functional changes in ...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/j.ejheart.2004.04.008
更新日期:2005-01-01 00:00:00
abstract:AIMS:Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.212
更新日期:2015-02-01 00:00:00
abstract:AIMS:To characterize the prevalence and clinical relevance of malnutrition in patients undergoing transcatheter tricuspid valve edge-to-edge repair (TTVR). METHODS AND RESULTS:Overall, 86 consecutive patients (mean age 78 ± 7 years) with moderate-to-severe tricuspid regurgitation (TR) at prohibitive surgical risk were...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.1752
更新日期:2020-10-01 00:00:00
abstract:BACKGROUND:Cognitive impairment is common among chronic heart failure (CHF) patients. AIMS:To determine the prognostic significance of cognitive impairment in patients participating in a randomized study of a CHF management program (CHF-MP). METHODS:CHF patients were randomized to a CHF-MP (n=100) or usual care (n=10...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/j.ejheart.2005.11.013
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:The angiotensin II type 2 (AT2) receptor is thought to play a role in cardiovascular disorders such as neointima formation after vascular injury, cardiac hypertrophy and myocardial infarction (MI). Recently, the biallelic polymorphism G + 1675A in intron 1 of the AT2 receptor gene has been associated with le...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/s1388-9842(02)00168-x
更新日期:2002-12-01 00:00:00
abstract:AIMS:Heart failure (HF) with normal or preserved left ventricular (LV) ejection fraction (HFPEF) has been reported to be associated with similar outcome as HF with reduced EF (HFREF) in registry-based and epidemiological analyses, but many of these studies excluded patients who did not have EF measurements. Conversely,...
journal_title:European journal of heart failure
pub_type: 杂志文章,meta分析
doi:10.1093/eurjhf/hfp103
更新日期:2009-09-01 00:00:00
abstract:AIMS:Modulation of vagal tone using electrical vagal nerve stimulation or pharmacological acetylcholinesterase inhibition by donepezil exerts beneficial effects in an animal model of chronic heart failure (CHF). Considering different treatment mechanisms underlying renin-angiotensin system (RAS) suppression and parasym...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.164
更新日期:2014-10-01 00:00:00