CBS 2019
CBSMD教育中心
中 文

血流动力学与动脉粥样硬化

Abstract

Recommended Article

Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study Low Endothelial Shear Stress Predicts Evolution to High-Risk Coronary Plaque Phenotype in the Future: A Serial Optical Coherence Tomography and Computational Fluid Dynamics Study Coronary Microcirculation in Ischemic Heart Disease Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation Angiographic derived endothelial shear stress: a new predictor of atherosclerotic disease progression Flow-Regulated Endothelial S1P Receptor-1 Signaling Sustains Vascular Development Evolving understanding of the heterogeneous natural history of individual coronary artery plaques and the role of local endothelial shear stress Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO pathway
|<< 1 2 3 >>|

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 REGISTRATION

> CBS 2019 PROGRAM

> CBS 2019 CALL FOR SCIENCE

> CBS 2019 SPOTLIGHTS

 CBSMD

> CBSMD WEBSITE REGISTRATION

> EDUCATION CENTER

> RECOMMANDED PAPER

> TOP 10 RESEARCH PAPER

> PRE-READING

CBS 2019 CBS 2019 FACULTY Education Resource CBSMD Scientific Library
Copyright ⓒ CBS MD Nanjing China. All rights reserved. 京ICP备16025898号-11
联系我们| Top