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Bo L.,CAS Institute of Zoology | Su-Ling D.,CAS Institute of Zoology | Fang L.,CAS Institute of Zoology | Lu-Yu Z.,CAS Institute of Zoology | And 4 more authors.
Cell Death and Differentiation | Year: 2014

Autophagy is required for the maintenance of cardiomyocytes homeostasis. However, the abnormal autophagy could lead to the development of heart failure. Autophagy is enhanced during myocardial ischemia/reperfusion; it remains to elucidate the molecular regulation of autophagy. We report here that miR-325, ARC and E2F1 constitute an axis that regulates autophagy. Our results showed that miR-325 expression is upregulated upon anoxia/reoxygenation and ischemia/reperfusion. Cardiomyocyte-specific overexpression of the miR-325 potentiates autophagic responses and myocardial infarct sizes, whereas knockdown of miR-325 inhibited autophagy and cell death. We searched for the downstream mediator of miR-325 and identified that ARC is a target of miR-325. ARC transgenic mice could attenuate autophagy and myocardial infarction sizes upon pressure-overload-induced heart failure, whereas ARC null mice exhibited an increased autophagic accumulation in the heart. The suppression of ARC by miR-325 led to its inability to repress autophagic program. In exploring the molecular mechanism by which miR-325 expression is regulated, our results revealed that the transcription factor E2F1 contributed to promote miR-325 expression. E2F1 null mice demonstrated reduced autophagy and myocardial infarction sizes upon ischemia/reperfusion. Our present study reveals a novel autophagic regulating model that is composed of E2F1, miR-325 and ARC. Modulation of their levels may provide a new approach for tackling cardiac failure. © 2014 Macmillan Publishers Limited All rights reserved. Source


Han Y.,General Hospital of Shenyang Military Command | Xu B.,National Center for Cardiovascular Diseases | Jing Q.,General Hospital of Shenyang Military Command | Lu S.,Capital Medical University | And 7 more authors.
JACC: Cardiovascular Interventions | Year: 2014

Objectives: The aim of this study was to investigate the hypothesis that a novel biodegradable polymer-coated, cobalt-chromium (CoCr), sirolimus-eluting stent (BP-SES) is noninferior in safety and efficacy outcomes compared with a durable polymer (DP)-SES. Background: No randomized trials have the compared safety and efficacy of BP-SES versus DP-SES on similar CoCr platforms, thereby isolating the effect of the polymer type. Methods: In this prospective, single-blind, randomized trial conducted at 32 Chinese sites, 2,737 patients eligible for coronary stenting were treated with BP- or DP-SES in a 2:1 ratio. The primary endpoint was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. Secondary endpoints included TLF components, and definite/probable stent thrombosis. Results: At 12 months, the difference in the primary endpoint of TLF between BP-SES (6.3%) and DP-SES (6.1%) groups was 0.25% (95% confidence interval: -1.67% to 2.17%, p for noninferiority = 0.0002), demonstrating noninferiority of BP-SES to DP-SES. Individual TLF components of cardiac death (0.7% vs. 0.6%, p = 0.62), target vessel myocardial infarction (3.6% vs. 4.3%, p = 0.39), and clinically indicated target lesion revascularization (2.6% vs. 2.2%, p = 0.50) were similar, as were low definite/probable stent thrombosis rates (0.4% vs. 0.6%, p = 0.55). Conclusions: In this large-scale real-world trial, BP-SES was noninferior to DP-SES for 1-year TLF. (Evaluate Safety and Effectiveness of the Tivoli ® DES and the Firebird ® DES for Treatment of Coronary Revascularization;. NCT01681381). © 2014 by the American College of Cardiology Foundation. Source


Kjeldsen S.,University of Oslo | Feldman R.D.,University of Western Ontario | Lisheng L.,National Center for Cardiovascular Diseases | Mourad J.-J.,Avicenne University Hospital | And 5 more authors.
Drugs | Year: 2014

Despite the availability of effective pharmacological treatments to aid the control of blood pressure, the global rate of uncontrolled blood pressure remains high. As such, further measures are required to improve blood pressure control. Recently, several national and international guidelines for the management of hypertension have been published. These aim to provide easily accessible information for healthcare professionals and patients to aid the diagnosis and treatment of hypertension. In this review, we have compared new and current guidelines from the American and International Societies of Hypertension; the American Heart Association, American College of Cardiology and the US Center for Disease Control and Prevention; the panel appointed to the Eighth Joint National Committee; the European Societies of Hypertension and Cardiology; the French Society of Hypertension; the Canadian Hypertension Education Program; the National Institute for Health and Clinical Excellence (UK); the Taiwan Society of Cardiology and the Chinese Hypertension League. We have identified consensus opinion regarding best practises for the management of hypertension and have highlighted any discrepancies between the recommendations. In general there is good agreement between the guidelines, however, in some areas, such as target blood pressure ranges for the elderly, further trials are required to provide sufficient high-quality evidence to form the basis of recommendations. © 2014 The Author(s). Source


Zhang H.,National Center for Cardiovascular Disease | Zhang H.,Chinese Academy of Sciences | Zhang H.,National Center for Cardiovascular Diseases | Gong D.-X.,National Center for Cardiovascular Disease | And 6 more authors.
European Heart Journal | Year: 2012

Aims About 40 of East Asians carry an aldehyde dehydrogenase-2 (*)2 (ALDH2 (*)2) allele, and the influence of the ALDH2 (*)2 allele on human cardioprotection has not been studied. This study was designed to evaluate the effect of ALDH2 (*)2 allele on cardioprotection of patients with congenital heart diseases after open-heart surgery.Methods and resultsThe right atrial appendage was harvested before performing cardiopulmonary bypass in cyanotic and acyanotic congenital heart disease groups (n 20 per group). Tissues were assayed to determine the impact of cyanosis on metabolic remodelling. A prospective cohort of Tetralogy of Fallot (TOF) patients (n 118) was recruited to investigate the influence of the ALDH2 (*)2 allele on cardioprotection after surgical repair. Myocardium samples were dissected after cardioplegia. ALDH2 activity, oxidative stress and glutathione (GSH) levels, and activating transcription factor-4 (ATF4) were analysed. After genotyping and grouping, all of the experimental and clinical results were compared between ALDH2 (*)2 carriers and non-carriers.Cyanosis inhibited ALDH2 activity and led to aldehyde accumulation in ALDH2 (*)2 carriers. This accumulation in turn increased expression of ATF4 and resulted in larger myocardium GSH pools. The differences in ALDH2 activity and GSH level between carriers and non-carriers disappeared during cardioplegic arrest, and more aldehydes accumulated in the non-carriers. Consequently, ALDH2 (*)2 carriers showed lower postoperative troponin I, inotrope score, and shorter postoperative length of ICU and hospital stay. Conclusions ALDH2 (*)2 carriers with cyanotic congenital heart disease were associated with an induced metabolic remodelling phenotype and a compensatory myocardium GSH pool. When ALDH2 activity was impaired during open-heart surgery, this larger GSH pool could lead to unexpectedly better cardioprotection. This may aid in the prediction of cardioprotection outcomes and identification of individualized cardioprotective strategies. © 2012 The Author. Source


Han Y.,General Hospital of Shenyang Military Command | Guo J.,Capital Medical University | Zheng Y.,Jilin University | Zang H.,No. 463 Hospital of PLA | And 20 more authors.
JAMA - Journal of the American Medical Association | Year: 2015

Importance: The safety and efficacy of bivalirudin compared with heparin with or without glycoprotein IIb/IIIa inhibitors in patients with acutemyocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are uncertain. OBJECTIVE To determine if bivalirudin is superior to heparin alone and to heparin plus tirofiban during primary PCI. Design, Setting, and Participants: Multicenter, open-label trial involving 2194 patients with AMI undergoing primary PCI at 82 centers in China between August 2012 and June 2013. Interventions: Patients were randomly assigned to receive bivalirudin with a post-PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a post-PCI infusion (n = 730). Among patients treated with bivalirudin, a postprocedure 1.75mg/kg/h infusion was administered for a median of 180 minutes (IQR, 148-240 minutes). Main outcomes and Measures: The primary end pointwas 30-day net adverse clinical events, a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or bleeding. Additional prespecified safety end points included the rates of acquired thrombocytopenia at 30 days, and stent thrombosis at 30 days and 1 year. Results: Net adverse clinical events at 30 days occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67; 95%CI, 0.50-0.90; difference, -4.3%, 95%CI, -7.5%to -1.1%; P = .008); and 124 patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin vs heparin plus tirofiban, 0.52; 95%CI, 0.39-0.69; difference, -8.1%, 95%CI, -11.6%to -4.7%; P < .001). The 30-day bleeding rate was 4.1%for bivalirudin, 7.5%for heparin, and 12.3%for heparin plus tirofiban (P < .001). There were no statistically significant differences between treatments in the 30-day rates of major adverse cardiac or cerebral events (5.0%for bivalirudin, 5.8% for heparin, and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6%vs 0.9%vs 0.7%, respectively, P = .77), acquired thrombocytopenia (0.1%vs 0.7%vs 1.1%; P = .07), or in acute (<24-hour) stent thrombosis (0.3%in each group). At the 1-year follow-up, the results remained similar. Conclusions and Relevance: Among patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3-hour postprocedure PCI-dose infusion resulted in a decrease in net adverse clinical events compared with both heparin alone and heparin plus tirofiban. This finding was primarily due to a reduction in bleeding events with bivalirudin, without significant differences in major adverse cardiac or cerebral events or stent thrombosis. Source

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