Evidence map›Paper›PMID 25590961›Full record

ArticleInternational journal of cardiology2015

Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection.

Bin Yu, Ha Won Kim, Min Gong, Jingcai Wang, Ronald W Millard, Yigang Wang, Muhammad Ashraf, Meifeng Xu

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 294 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
294citing papers in PubMed, 5 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

294 citing papers in PubMed, 5 syntheses or guidelines pooled it, 474 citations in OpenAlex.

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234 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Bin YuDepartment of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
Ha Won KimDepartment of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
Min GongDepartment of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
Jingcai WangDepartment of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
Ronald W MillardDepartment of Pharmacology & Cell Biophysics, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
Yigang WangDepartment of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
Muhammad AshrafDepartment of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
Meifeng XuDepartment of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA. Electronic address: Meifeng.xu@uc.edu.
University of Cincinnati · US

Funding

Stem Cells in Cardiac Repair and AngiogenesisR37HL074272 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ASHRAF, MUHAMMAD · 2003 to 2013
$5.7M
MicroRNA as mediators of angiogenesis & ischemic myocardial repairR01HL114654 · NHLBI · UNIVERSITY OF CINCINNATI · PI ASHRAF, MUHAMMAD, XU, MEIFENG · 2012 to 2016
$2.5M
Wnt11 signaling in stem cell survival and cardiac regenerationR01HL105176 · NHLBI · UNIVERSITY OF CINCINNATI · PI ASHRAF, MUHAMMAD, JONES, WALTER KEITH · 2010 to 2014
$1.9M
NHLBI NIH HHS HL105176NHLBI NIH HHS HL114654NHLBI NIH HHS R01 HL105176NHLBI NIH HHS R01 HL114654NHLBI NIH HHS R37 HL074272NHLBI NIH HHS R37HL 074272
6 · The paper itself

Abstract

backgroundExosomes play an important role in intercellular signaling and exert regulatory function by carrying bioactive molecules. This study investigated (1) the cardioprotective capabilities of exosomes derived from mesenchymal stem cells (MSCs) overexpressing GATA-4 (MSC(GATA-4)) and (2) its underlying regulatory mechanisms for expression of target proteins in recipient cells. METHODS AND

resultsExosomes were isolated and purified from MSC(GATA-4) (Exo(GATA-4)) and control MSCs (Exo(Null)). Cell injury was investigated in primary cultured rat neonatal cardiomyocytes (CM) and in the rat heart. Exosomes contributed to increased CM survival, reduced CM apoptosis, and preserved mitochondrial membrane potential in CM cultured under a hypoxic environment. Direct intramyocardial transplantation of exosomes at the border of an ischemic region following ligation of the left anterior descending coronary artery significantly restored cardiac contractile function and reduced infarct size. Real-time PCR revealed that several anti-apoptotic miRs were highly expressed in Exo(GATA-4). Rapid internalization of Exo(GATA-4) by CM was documented using time-lapse imaging. Subsequent expression of these miRs, particularly miR-19a was higher in CM and in the myocardium treated with Exo(GATA-4) compared to those treated with Exo(Null). The enhanced protective effects observed in CM were diminished by the inhibition of miR-19a. The expression level of PTEN, a predicted target of miR-19a, was reduced in CM treated with Exo(GATA-4), which resulted in the activation of the Akt and ERK signaling pathways.

conclusionsExo(GATA-4) upon transplantation in the damaged tissue mediate protection by releasing multiple miRs responsible for activation of the cell survival signaling pathway.

Indexed as

ApoptosisGene Expression RegulationAnimalsCells, CulturedCell SurvivalExosomesGATA4 Transcription FactorMesenchymal Stem CellsMesenchymal Stem Cell TransplantationMicroRNAsMyocardial InfarctionMyocytes, CardiacRatsReal-Time Polymerase Chain ReactionRNAGATA4 Transcription FactorMicroRNAsRNABone marrow stem cellsCardioprotectionExosomesGATA-4MiR transferTarget proteins

Identifiers

PMID25590961
PMCPMC4382384
OpenAlexW2090335937

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.