Abstract:
OBJECTIVES:we tested the hypothesis that bi-directional, gene-targeted regulation of cardiomyocyte cyclic guanosine monophosphate-selective phosphodiesterase type 5 (PDE5) influences maladaptive remodeling in hearts subjected to sustained pressure overload. BACKGROUND:PDE5 expression is up-regulated in human hypertrophied and failing hearts, and its inhibition (e.g., by sildenafil) stimulates protein kinase G activity, suppressing and reversing maladaptive hypertrophy, fibrosis, and contractile dysfunction. Sildenafil is currently being clinically tested for the treatment of heart failure. However, researchers of new studies have questioned the role of myocyte PDE5 and protein kinase G (PKG) to this process, proposing alternative targets and mechanisms. METHODS:mice with doxycycline-controllable myocyte-specific PDE5 gene expression were generated (medium transgenic [TG] and high TG expression lines) and subjected to sustained pressure overload. RESULTS:Rest myocyte and heart function, histology, and molecular profiling were normal in both TG lines versus controls at 2 months of age. However, upon exposure to pressure overload (aortic banding), TG hearts developed more eccentric remodeling, maladaptive molecular signaling, depressed function, and amplified fibrosis with up-regulation of tissue growth factor signaling pathways. PKG activation was inhibited in TG myocytes versus controls. After establishing a severe cardiomyopathic state, high-TG mice received doxycycline to suppress PDE5 expression/activity only in myocytes. This in turn enhanced PKG activity and reversed all previously amplified maladaptive responses, despite sustained pressure overload. Sildenafil was also effective in this regard. CONCLUSIONS:these data strongly support a primary role of myocyte PDE5 regulation to myocardial pathobiology and PDE5 targeting therapy in vivo and reveal a novel mechanism of myocyte-orchestrated extracellular matrix remodeling via PDE5/cyclic guanosine monophosphate-PKG regulatory pathways.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Zhang M,Takimoto E,Hsu S,Lee DI,Nagayama T,Danner T,Koitabashi N,Barth AS,Bedja D,Gabrielson KL,Wang Y,Kass DAdoi
10.1016/j.jacc.2010.08.612subject
Has Abstractpub_date
2010-12-07 00:00:00pages
2021-30issue
24eissn
0735-1097issn
1558-3597pii
S0735-1097(10)03897-0journal_volume
56pub_type
杂志文章abstract:OBJECTIVES:This study prospectively evaluated whether early assessment with adenosine thallium-201 tomography could better refine risk stratification on the basis of absolute extent of myocardial ischemia in postinfarction patients in clinically stable condition. BACKGROUND:Postinfarction patients are at increased ris...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(95)00016-W
更新日期:1995-05-01 00:00:00
abstract::The adequacy of two-dimensional echocardiography during right atrial pacing for the detection and characterization of coronary artery stenosis was examined in 10 closed chest dogs. Pacing at successively higher rates up to 210 beats/min was carried out in the control state and again during a 70% left anterior descendi...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(83)80309-x
更新日期:1983-10-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to compare the frequency of angiographic restenosis and clinical events between a paclitaxel-eluting stent (PES) and a similar bare-metal stent (BMS) in saphenous vein graft (SVG) lesions. BACKGROUND:There are conflicting and mostly retrospective data on outcomes after drug-eluting...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jacc.2008.11.029
更新日期:2009-03-17 00:00:00
abstract::Homocysteine has been implicated in promoting atherosclerotic and thrombotic vascular disease. During the last decade, the utility of homocysteine in predicting risk for atherothrombotic vascular disease has been evaluated in several observational studies in a large number of patients. These studies show that the over...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2006.04.086
更新日期:2006-09-05 00:00:00
abstract:OBJECTIVES:This study was designed to determine whether atrial natriuretic peptide and skeletal alpha-actin messenger RNAs (mRNAs) are co-localized in ventricular myocytes of patients with dilated cardiomyopathy. BACKGROUND:Atrial natriuretic peptide and skeletal alpha-actin are known as augmented genes with cardiac h...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(95)00145-p
更新日期:1995-07-01 00:00:00
abstract:BACKGROUND:Circulating high-density lipoprotein particle (HDL-P) subfractions impact atherogenesis, inflammation, and endothelial function, all of which are implicated in the pathobiology of heart failure (HF). OBJECTIVES:The authors sought to identify key differences in plasma HDL-P subfractions between patients with...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2018.10.059
更新日期:2019-01-22 00:00:00
abstract::Irregularity of the ventricular rhythm is a hallmark of patients with atrial fibrillation, yet the genesis of the irregularity is not yet fully understood. The role of the atrioventricular (AV) node in determining the irregularity of the ventricular response to atrial fibrillation was investigated by comparing the fre...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(88)92610-1
更新日期:1988-11-01 00:00:00
abstract:OBJECTIVES:This study was designed to assess the safety and efficacy of intravenously administered sonicated human serum albumin for enhancing echocardiographic delineation of the left ventricular endocardium and improving assessment of wall motion in patients with incomplete depiction of noncontrast echocardiography. ...
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:10.1016/0735-1097(93)90562-f
更新日期:1993-11-01 00:00:00
abstract::The knowledge and treatment of cardiology as practiced circa 1950 is discussed as abstracted from authoritative textbooks of that time and other sources. Advances in treatment and diagnostic techniques since 1950 are presented. Dramatic changes in cardiology have come at the expense of bedside cardiology which needs t...
journal_title:Journal of the American College of Cardiology
pub_type: 历史文章,杂志文章
doi:10.1016/s0735-1097(99)00027-3
更新日期:1999-04-01 00:00:00
abstract::Members of the vascular endothelial growth factor (VEGF) family are among the most powerful modulators of vascular biology. They regulate vasculogenesis, angiogenesis, and vascular maintenance during embryogenesis and in adults. Because of their profound effects on blood vessels, VEGFs have received much attention reg...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2006.09.053
更新日期:2007-03-13 00:00:00
abstract:OBJECTIVES:This study compared the efficacy and safety of two antitachycardia pacing algorithms in the treatment of ventricular tachycardia. BACKGROUND:There is agreement that antitachycardia pacing should be adapted to tachycardia rate and be delivered in a burst, but the ideal pacing pattern is not well understood. ...
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)90318-u
更新日期:1993-05-01 00:00:00
abstract:OBJECTIVES:To show the effect of clinical, angio and demographic traits on late survival of Coronary Artery Surgery Study (CASS) patients following coronary artery bypass grafting (CABG) and introduce Hazard Function analysis to CASS survival data. METHODS:Patients were reached by mail survey with 94% response. By Nat...
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/s0735-1097(98)00563-4
更新日期:1999-02-01 00:00:00
abstract::Effects of coronary angioplasty on myocardial flow reserve have been difficult to characterize noninvasively because conventional imaging techniques cannot quantitate blood flow in absolute terms. The effects of coronary angioplasty on myocardial perfusion and perfusion reserve were delineated with positron emission t...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(90)90186-s
更新日期:1990-01-01 00:00:00
abstract::The management of anticoagulant therapy in patients with atrial fibrillation undergoing electrical cardioversion remains controversial, largely because of inadequate studies demonstrating risk or benefit, a relatively inconvenient anticoagulation management strategy and the increasing use of transesophageal echocardio...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/0735-1097(94)90443-x
更新日期:1994-02-01 00:00:00
abstract:OBJECTIVES:This study sought to assess the long-term predictive value and net reclassification for risk of cardiovascular disease (CVD) of biomarkers reflecting oxidation-specific epitopes (OSEs). BACKGROUND:OSEs are immunogenic, proinflammatory, and proatherogenic. The long-term predictive value and net reclassificat...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2012.08.979
更新日期:2012-11-20 00:00:00
abstract:BACKGROUND:Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which is associated with accelerated atherogenesis and increased cardiovascular risk. OBJECTIVES:This study used (18)F-fluorodeoxygluco...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2014.01.088
更新日期:2014-10-07 00:00:00
abstract:BACKGROUND:Limited intimal tears (LITs) of the aorta (Class 3 dissection variant) are the least common form of aortic pathology in patients presenting with acute aortic syndrome (AAS). LITs are difficult to detect on imaging and may be underappreciated. OBJECTIVES:This study sought to describe the frequency, pathology...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2018.03.531
更新日期:2018-06-19 00:00:00
abstract:OBJECTIVES:The purpose of this study is to demonstrate the technical success of carotid artery stenting in acute extracranial internal carotid artery (ICA) occlusion as well as the benefit in clinical outcome. BACKGROUND:Stroke caused by acute occlusion of the ICA is associated with a significant level of morbidity an...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2011.08.044
更新日期:2011-11-29 00:00:00
abstract:OBJECTIVES:The contribution of nitric oxide (NO) and adenosine to the increase in coronary blood flow (CBF) induced by cardiac pacing was investigated in 28 subjects with angiographically normal coronary arteries with and without one or more risk factors for atherosclerosis. BACKGROUND:NO and adenosine are important i...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(98)00095-3
更新日期:1998-05-01 00:00:00
abstract:OBJECTIVES:This study sought to examine the effect of oral metformin (Mf) therapy on endothelialization in the setting of drug-eluting stents (DES). BACKGROUND:Mf is a commonly used therapy in diabetic patients receiving DES. Mf and locally eluted mammalian target of rapamycin (mTOR) inhibitors used in DES have conver...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2012.12.018
更新日期:2013-03-05 00:00:00
abstract:OBJECTIVES:The purpose of this study was to determine the mechanisms of sudden death (SD) in patients with ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) treated with an implantable cardioverter defibrillator (ICD). BACKGROUND:Despite ICD therapy, some patients with VT/VF still...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(02)01784-9
更新日期:2002-04-17 00:00:00
abstract:OBJECTIVES:We examined the extent of fibrotic changes in the left atrium of cardiomyopathic human hearts and investigated the relation of mechanical overload caused by left ventricular dysfunction to fibrosis of the left atrium. BACKGROUND:Left atrial dysfunction in dilated cardiomyopathy may contribute to progression...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(94)00529-y
更新日期:1995-04-01 00:00:00
abstract:BACKGROUND:This study demonstrated the safety and effectiveness of baroreflex activation therapy (BAT) in patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES:The BeAT-HF (Baroreflex Activation Therapy for Heart Failure) trial was a multicenter, prospective, randomized, controlled trial; subj...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jacc.2020.05.015
更新日期:2020-07-07 00:00:00
abstract:OBJECTIVES:This study sought to assess the diagnostic value of optical coherence tomography (OCT) in patients with suspected spontaneous coronary artery dissection (SCAD). BACKGROUND:SCAD is a rare but challenging clinical entity. METHODS:Following a prospective protocol, OCT was performed in 17 consecutive patients ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2011.08.082
更新日期:2012-03-20 00:00:00
abstract:OBJECTIVES:We compared left ventricular (LV) systolic and diastolic function during right ventricular (RV), LV, and biventricular (BiV) pacing in patients with narrow QRS duration with and without LV dysfunction. BACKGROUND:The optimal RV pacing lead location for patients with a standard indication for ventricular pac...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2006.04.099
更新日期:2006-10-17 00:00:00
abstract::Pre-clinical diastolic dysfunction (PDD) has been broadly defined as left ventricular diastolic dysfunction without the diagnosis of congestive heart failure (HF) and with normal systolic function. PDD is an entity that remains poorly understood, yet has definite clinical significance. Although few original studies ha...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2013.10.063
更新日期:2014-02-11 00:00:00
abstract:OBJECTIVES:We investigated the effects of short-term tezosentan treatment on cardiac function, pulmonary edema and long-term evolution of heart failure (HF) in a rat model of myocardial infarction (MI). BACKGROUND:Endothelin (ET) may play a major role in the progression from MI to HF. Tezosentan is a new dual ET(A)/ET...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(01)01692-8
更新日期:2002-01-02 00:00:00
abstract::A new, predominantly single chain preparation of recombinant tissue-type plasminogen activator was evaluated to determine coronary thrombolytic efficacy in 100 patients with acute myocardial infarction. At 3.6 +/- 1.2 hours (mean +/- SD) from symptom onset, patients received either intravenous tissue plasminogen activ...
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/s0735-1097(87)80457-6
更新日期:1987-06-01 00:00:00
abstract:OBJECTIVES:We hypothesized that combining biphasic waveform and sequential pulse defibrillation techniques would lower the defibrillation threshold of a nonthoracotomy lead system in humans below that obtained with biphasic or sequential pulse defibrillation alone. BACKGROUND:Previous studies have shown that sequentia...
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(94)90413-8
更新日期:1994-02-01 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