CBS 2019
CBSMD教育中心
English

充血性心力衰竭

科研文章

荐读文献

Lower Risk of Heart Failure and Death in Patients Initiated on SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study Improving the Use of Primary Prevention Implantable Cardioverter-Defibrillators Therapy With Validated Patient-Centric Risk Estimates Progression of Device-Detected Subclinical Atrial Fibrillation and the Risk of Heart Failure Good response to tolvaptan shortens hospitalization in patients with congestive heart failure Respiratory Syncytial Virus and Associations With Cardiovascular Disease in Adults Can We Use the Intrinsic Left Ventricular Delay (QLV) to Optimize the Pacing Configuration for Cardiac Resynchronization Therapy With a Quadripolar Left Ventricular Lead? Cardiac Implantable Electronic Devices in Patients With Left Ventricular Assist Systems HFpEF: From Mechanisms to Therapies Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators - The RAID Trial Heart failure with preserved ejection fraction: from mechanisms to therapies
|<< 1 2 3 4 5 6 7 ...>>|

Original Research2019 Apr 10. [Epub ahead of print]

JOURNAL：Nature. Article Link

Nitrosative stress drives heart failure with preserved ejection fraction

Schiattarella GG, Altamirano F, Hill JA et al. Keywords: HFpEF; iNOS-driven dysregulation; IRE1α-XBP1 pathway; mechanism of cardiomyocyte dysfunction

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality for which there are no evidence-based therapies. Here we report that concomitant metabolic and hypertensive stress in mice-elicited by a combination of high-fat diet and inhibition of constitutive nitric oxide synthase using Nω-nitro-L-arginine methyl ester (L-NAME)-recapitulates the numerous systemic and cardiovascular features of HFpEF in humans. Expression of one of the unfolded protein response effectors, the spliced form of X-box-binding protein 1 (XBP1s), was reduced in the myocardium of our rodent model and in humans with HFpEF. Mechanistically, the decrease in XBP1s resulted from increased activity of inducible nitric oxide synthase (iNOS) and S-nitrosylation of the endonuclease inositol-requiring protein 1α (IRE1α), culminating in defective XBP1 splicing. Pharmacological or genetic suppression of iNOS, or cardiomyocyte-restricted overexpression of XBP1s, each ameliorated the HFpEF phenotype. We report that iNOS-driven dysregulation of the IRE1α-XBP1 pathway is a crucial mechanism of cardiomyocyte dysfunction in HFpEF.

>CBS CBS 2019

> CBS 2019

> CBS 2019 注册

> CBS 2019 会议日程

> CBS 2019 学术征集

> CBS 2019 热点

 CBSMD

> CBSMD 网站注册

> 教育中心

> 荐读文献

> Top 10 阅读文献

> 文献导读
CBS 2019 CBS 2019 主席团 教育中心 科研动态
Copyright ⓒ CBS MD Nanjing China. All rights reserved. 京ICP备16025898号-11
联系我们| Top