Abstract:
OBJECTIVES:The goal of this pre-clinical study was to assess the therapeutic efficacy of doxycycline (Doxy) for desmin-related cardiomyopathy (DRC) and to elucidate the potential mechanisms involved. BACKGROUND:DRC, exemplifying cardiac proteinopathy, is characterized by intrasarcoplasmic protein aggregation and cardiac insufficiency. No effective treatment for DRC is available presently. Doxy was shown to attenuate aberrant intranuclear aggregation and toxicity of misfolded proteins in noncardiac cells and animal models of other proteinopathies. METHODS:Mice and cultured neonatal rat cardiomyocytes with transgenic (TG) expression of a human DRC-linked missense mutation R120G of αB-crystallin (CryAB(R120G)) were used for testing the effect of Doxy. Doxy was administered via drinking water (6 mg/ml) initiated at 8 or 16 weeks of age. RESULTS:Doxy treatment initiated at 16 weeks of age significantly delayed the premature death of CryAB(R120G) TG mice, with a median lifespan of 30.4 weeks (placebo group, 25 weeks; p < 0.01). In another cohort of CryAB(R120G) TG mice, Doxy treatment initiated at 8 weeks of age significantly attenuated cardiac hypertrophy in 1 month. Further investigation revealed that Doxy significantly reduced the abundance of CryAB-positive microscopic aggregates, detergent-resistant CryAB oligomers, and total ubiquitinated proteins in CryAB(R120G) TG hearts. In cell culture, Doxy treatment dose-dependently suppressed the formation of both microscopic protein aggregates and detergent-resistant soluble CryAB(R120G) oligomers and reversed the up-regulation of p62 protein induced by adenovirus-mediated CryAB(R120G) expression. CONCLUSIONS:Doxy suppresses CryAB(R120G)-induced aberrant protein aggregation in cardiomyocytes and prolongs CryAB(R120G)-based DRC mouse survival.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Zheng H,Tang M,Zheng Q,Kumarapeli AR,Horak KM,Tian Z,Wang Xdoi
10.1016/j.jacc.2010.01.075subject
Has Abstractpub_date
2010-10-19 00:00:00pages
1418-26issue
17eissn
0735-1097issn
1558-3597pii
S0735-1097(10)03507-2journal_volume
56pub_type
杂志文章abstract::In 10 patients with moderate to severe hypertension, the hemodynamic effects of ergometric exercise and nicardipine, a dihydropyridine calcium channel antagonist, were characterized under basal conditions and after 1 week of therapy. The responses of plasma renin activity and catecholamines were also assessed. Nicardi...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(87)80209-7
更新日期:1987-09-01 00:00:00
abstract:OBJECTIVES:This study was performed to validate the accuracy of color flow vena contracta (VC) measurements of aortic regurgitation (AR) severity by comparing them to simultaneous intraoperative flow probe measurements of regurgitant fraction (RgF) and regurgitant volume (RgV). BACKGROUND:Color Doppler imaging of the ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(01)01114-7
更新日期:2001-04-01 00:00:00
abstract::Hemodynamic stress testing was performed in four calves with a chronically implanted left ventricular assist device consisting of a double-valved pump interposed between the left ventricular apex and the descending thoracic aorta. The device was powered either pneumatically (n = 1) or with a transcutaneous energy tran...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(91)90521-a
更新日期:1991-12-01 00:00:00
abstract:OBJECTIVES:This study sought to determine the outcome of aortic valve replacement for aortic regurgitation complicated by extreme left ventricular dilation. BACKGROUND:Aortic valve replacement has been recommended in aortic regurgitation with extreme left ventricular dilation (diastolic dimension >/= 80 mm), but extre...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(95)00525-0
更新日期:1996-03-01 00:00:00
abstract:OBJECTIVES:We performed a meta-analysis of randomized trials that enrolled ST-segment elevation myocardial infarction patients treated with fibrinolysis to assess the potential benefits of: 1) rescue percutaneous coronary intervention (PCI) versus no PCI; 2) systematic and early (< or =24 h) PCI versus delayed or ische...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,meta分析
doi:10.1016/j.jacc.2006.03.064
更新日期:2006-10-03 00:00:00
abstract:OBJECTIVES:This study evaluated how variations in atrioventricular (AV) delay affect hemodynamic function in patients with refractory heart failure being supported with intravenous inotropic and intravenous or oral inodilating agents. BACKGROUND:Although preliminary data have suggested that dual-chamber pacing with sh...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(97)00307-0
更新日期:1997-11-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to investigate the effect of renin-angiotensin system blockade on outcomes in patients with aortic regurgitation (AR). BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors have the potential to reduce afterload, blunt left ventricular wall stress, and limit left ventricular di...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2011.07.043
更新日期:2011-11-08 00:00:00
abstract:BACKGROUND:High systolic blood pressure (SBP) increases cardiac afterload, whereas low diastolic blood pressure (DBP) may lead to impaired coronary perfusion. Thus, wide pulse pressure (high systolic, low diastolic [HSLD]) may contribute to myocardial ischemia and also be a predictor of adverse cardiovascular events. ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2019.03.493
更新日期:2019-06-11 00:00:00
abstract:OBJECTIVES:We evaluated the short- and long-term effects of flosequinan in 47 patients with severe heart failure despite ongoing captopril treatment. BACKGROUND:There have been no previous evaluations of the long-term hemodynamic effects of any direct-acting vasodilator in patients with heart failure receiving an angi...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0735-1097(93)90404-o
更新日期:1993-10-01 00:00:00
abstract:BACKGROUND:Guidelines strongly recommend patients with heart failure with reduced ejection fraction (HFrEF) be treated with multiple medications proven to improve clinical outcomes, as tolerated. The degree to which gaps in medication use and dosing persist in contemporary outpatient practice is unclear. OBJECTIVES:Th...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2018.04.070
更新日期:2018-07-24 00:00:00
abstract:OBJECTIVES:To determine how well recently developed multivariables scores assess for all-cause mortality in patients with suspected coronary disease presenting for exercise electrocardiography (ExECG). BACKGROUND:Recently revised American College of Cardiology/American Heart Association guidelines for ExECG have sugge...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(03)00837-4
更新日期:2003-09-03 00:00:00
abstract::It has been shown that streptokinase administration at the time of acute myocardial infarction reduces mortality significantly, and that this reduction in mortality should be related to salvage of jeopardized myocardium and preservation of left ventricular function. To better define the relation between thrombolytic t...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0735-1097(89)90409-9
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND:Although oral P2Y12 inhibitors are key in the management of patients with non-ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined. OBJECTIVES:The purpose of this study was to compare downstream and upstream oral P2Y12 inhibitors administration strateg...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2020.08.053
更新日期:2020-11-24 00:00:00
abstract:OBJECTIVES:The purpose of this study was to examine the effects of glycoprotein (GP) IIb/IIIa antagonists (abciximab, eptifibatide, and tirofiban) and other inhibitors on translocation of CD40L from intraplatelet stores to the platelet surface and on the release of soluble CD40L (sCD40L) from platelets. BACKGROUND:CD4...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2003.12.055
更新日期:2004-06-16 00:00:00
abstract:OBJECTIVES:We investigated the value of reactive hyperemia peripheral arterial tonometry (RH-PAT) as a noninvasive tool to identify individuals with coronary microvascular endothelial dysfunction. BACKGROUND:Coronary endothelial dysfunction, a systemic disorder, represents an early stage of atherosclerosis; RH-PAT is ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2004.08.062
更新日期:2004-12-07 00:00:00
abstract:BACKGROUND:Prolonged heart rate-corrected QT interval on electrocardiograms (ECGs) is associated with increased risk of myocardial infarction and cardiovascular disease (CVD)-related deaths in patients with prevalent coronary heart disease. OBJECTIVES:This study sought to examine the prognostic association between the...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2014.08.039
更新日期:2014-11-18 00:00:00
abstract:BACKGROUND:Subclinical inflammation mediated in part by interleukin (IL)-1β participates in peripheral insulin resistance and impaired pancreatic insulin secretion. OBJECTIVES:The authors tested the hypothesis that the IL-1β inhibitor canakinumab reduces incident diabetes. METHODS:The authors randomized 10,061 patien...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2018.03.002
更新日期:2018-05-29 00:00:00
abstract:BACKGROUND:Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2015.04.071
更新日期:2015-07-14 00:00:00
abstract:OBJECTIVES:We tested the hypothesis that one health status measure, the Kansas City Cardiomyopathy Questionnaire (KCCQ), provides prognostic information independent of other clinical data in outpatients with heart failure (HF). BACKGROUND:Health status measures are used to describe a patient's clinical condition and h...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jacc.2005.11.021
更新日期:2006-02-21 00:00:00
abstract::Because of its enhanced activation of plasminogen in association with fibrin compared with free plasminogen, tissue-type plasminogen activator (t-PA) evoked excitement as a potentially useful pharmacologic activator of the fibrinolytic system. Initial studies in experimental animals and patients demonstrated that it i...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(87)80427-8
更新日期:1987-11-01 00:00:00
abstract:OBJECTIVES:The Total Ischemic Burden Bisoprolol Study (TIBBS) follow-up examined cardiac event rates in relation to transient ischemia and its treatment. BACKGROUND:It is unclear whether transient ischemia on the ambulatory electrocardiogram has prognostic implications in stable angina and whether medical treatment ca...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/0735-1097(96)00122-2
更新日期:1996-07-01 00:00:00
abstract:OBJECTIVES:We attempted to determine whether continuous wave Doppler backscatter power could be used to quantify mitral regurgitation. BACKGROUND:The power of a Doppler backscatter signal is proportional to the number of scatterers insonated and, hence, to the moving volume of blood. The relative power of the continuo...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(94)90016-7
更新日期:1994-09-01 00:00:00
abstract::The hypothesis that myocardial contrast echocardiography could be used to simultaneously assess coronary blood flow reserve and the size of the perfusion bed supplied by a coronary artery was examined in nine patients and six dogs. All patients were undergoing cardiac catheterization and had single vessel coronary art...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(88)90456-1
更新日期:1988-10-01 00:00:00
abstract:UNLABELLED:The relationship between renal insufficiency and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels remains unclear. We examined this relationship in the context of patients who presented to the emergency department of an urban tertiary care medical center with dyspnea. Even in the presence of r...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2005.08.051
更新日期:2006-01-03 00:00:00
abstract:OBJECTIVES:This study sought to determine the diagnostic accuracy of 64-slice computed tomographic coronary angiography (CTCA) to detect or rule out significant coronary artery disease (CAD). BACKGROUND:CTCA is emerging as a noninvasive technique to detect coronary atherosclerosis. METHODS:We conducted a prospective,...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.jacc.2008.08.058
更新日期:2008-12-16 00:00:00
abstract:OBJECTIVES:This study sought to examine patterns of follow-up invasive coronary angiography (ICA) and revascularization (REV) after coronary computed tomography angiography (CCTA). BACKGROUND:CCTA is a noninvasive test that permits direct visualization of the extent and severity of coronary artery disease (CAD). Post-...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jacc.2012.05.062
更新日期:2012-11-13 00:00:00
abstract::Alterations in the blood radioactivity affect ventricular volume calculations using count-based radionuclide ventriculography. To study this phenomenon, the effect of time, posture and supine exercise on blood radioactivity, red blood cell count and splenic radioactivity was evaluated. The red blood cell count, and bl...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(84)80178-3
更新日期:1984-05-01 00:00:00
abstract:OBJECTIVES:This study sought to investigate the efficacy and safety of catheter ablation for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFPEF). BACKGROUND:AF is a precipitating factor for clinical deterioration of HFPEF. METHODS:Catheter ablation for AF was performed in ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2013.07.020
更新日期:2013-11-12 00:00:00
abstract:OBJECTIVES:We evaluated the prognostic value of dipyridamole stress cardiovascular magnetic resonance imaging (CMR) in patients with chest pain and known or suspected coronary artery disease. BACKGROUND:Stress perfusion CMR has been incorporated in daily practice. Data on its prognostic value are preliminary. METHODS...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2007.06.016
更新日期:2007-09-18 00:00:00
abstract:OBJECTIVES:A subgroup analysis of the Valsartan Heart Failure Trial (Val-HeFT) was performed to evaluate the effects of the angiotensin II receptor blocker, valsartan, in the patients with chronic heart failure (HF) not receiving angiotensin-converting enzyme (ACE) inhibitors. BACKGROUND:The ACE inhibitors reduce mort...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(02)02304-5
更新日期:2002-10-16 00:00:00