CBS 2019
CBSMD教育中心
中 文

Acute Coronary Syndrom

Abstract

Recommended Article

Prevalence of Angina Among Primary Care Patients With Coronary Artery Disease Application of High-Sensitivity Troponin in Suspected Myocardial Infarction Risk Stratification Guided by the Index of Microcirculatory Resistance and Left Ventricular End-Diastolic Pressure in Acute Myocardial Infarction Intravenous Statin Administration During Myocardial Infarction Compared With Oral Post-Infarct Administration Incidence, predictors, and outcomes of DAPT disruption due to non-compliance vs. bleeding after PCI: insights from the PARIS Registry Use of Mechanical Circulatory Support Devices Among Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock Risk Factors Associated With Major Cardiovascular Events 1 Year After Acute Myocardial Infarction Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention
|<<... 21 22 23 24 25 26 27 ...>>|

Original ResearchFebruary 26, 2020

JOURNAL：Circulation. Article Link

Phosphoproteomic Analysis of Neonatal Regenerative Myocardium Revealed Important Roles of CHK1 via Activating mTORC1/P70S6K Pathway

Y Fan, XJ Guo, LS Wang et al. Keywords: regenerative myocardium

ABSTRACT

BACKGROUND - In mammalian, regenerative therapy after myocardial infarction (MI) is hampered by the limited regenerative capacity of adult heart, while a transient regenerative capacity is maintained in the neonatal heart. Systemic phosphorylation signaling analysis on ischemic neonatal myocardium might be helpful to identify key pathways involved in heart regeneration. We aimed to define kinase-substrate network in ischemic neonatal myocardium and identify key pathways involved in heart regeneration post ischemic insult.

 

METHODS - Quantitative phosphoproteomics profiling was performed on infarct border zone of neonatal myocardium, and kinase-substrate network analysis revealed 11 kinases with enriched substrates and upregulated phosphorylation levels including CHK1 kinase. The effect of CHK1 on cardiac regeneration was tested on ICR-CD1 neonatal and adult mice underwent apical resection or MI.

 

RESULTS - In vitro, CHK1 overexpression promoted, while CHK1 knockdown blunted cardiomyocyte (CM) proliferation. In vivo, inhibition of CHK1 hindered myocardial regeneration on resection border zone in neonatal mice. In adult MI mice, CHK1 overexpression on infarct border zone upregulated mTORC1/P70S6K pathway, promoted CM proliferation and improved cardiac function. Inhibiting mTOR activity by rapamycin blunted the neonatal CM proliferation induced by CHK1 overexpression in vitro.

 

CONCLUSIONS - Our study indicates that phosphoproteome of neonatal regenerative myocardium could help identify important signaling pathways involved in myocardial regeneration. CHK1 is found to be a key signaling responsible for neonatal regeneration. Myocardial overexpression of CHK1 could improve cardiac regeneration in adult hearts through activating mTORC1/P70S6K pathway, CHK1 might thus serve as a potential novel target in myocardial repair post MI.

>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