Evidence map›Paper›PMID 33742276›Full record

ArticleBasic research in cardiology2021

miR-106a-363 cluster in extracellular vesicles promotes endogenous myocardial repair via Notch3 pathway in ischemic heart injury.

Ji-Hye Jung, Gentaro Ikeda, Yuko Tada, Daniel von Bornstädt, Michelle R Santoso, Christine Wahlquist, Siyeon Rhee, Young-Jun Jeon, Anthony C Yu, Connor G O'brien and 5 more

Open access · greenAbstract readVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in Basic research in cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.7field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 53 citations in OpenAlex.

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  6. Extracellular vesicle therapeutics for cardiac repair.Journal of molecular and cellular cardiology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 2 countries.

Ji-Hye JungDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Gentaro IkedaDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Yuko TadaDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Daniel von BornstädtDepartment of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Michelle R SantosoDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Christine WahlquistStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Siyeon RheeDepartment of Biology, Stanford University, Stanford, CA, 94305, USA.
Young-Jun JeonDepartment of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Anthony C YuDepartment of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
Connor G O'brienDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Kristy Red-HorseDepartment of Biology, Stanford University, Stanford, CA, 94305, USA.
Eric A AppelDepartment of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
Mark MercolaStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Joseph WooDepartment of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Phillip C YangDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA. phillip@stanford.edu.ORCID http://orcid.org/0000-0002-6274-895X
Stanford University · USCardiovascular Institute of the South · USSungkyunkwan University · KR

Funding

MN Regional Cardiovascular Cell Therapy Clinical Res. Network: From AMI to PADUM1HL087394 · NHLBI · UNIVERSITY OF MINNESOTA · PI HENRY, TIMOTHY D · 2012 to 2018
$5.1M
Cell Characterization and Imaging for Regenerative Therapies in Ischemic DiseasesUM1HL113456 · NHLBI · STANFORD UNIVERSITY · PI YANG, PHILLIP CHUNG-MING · 2012 to 2018
$3.3M
Patient Oriented Research in Cardiovascular RegenerationK24HL130553 · NHLBI · STANFORD UNIVERSITY · PI YANG, PHILLIP CHUNG-MING · 2016 to 2020
$584k
Using Exosomes to Preserve Viability and Function in Anthracycline Induced Cardiomyopathy Patient Specific Cardiomyocytes After Exposure to DoxorubicinF32HL139046 · NHLBI · STANFORD UNIVERSITY · PI O'BRIEN, CONNOR · 2017 to 2018
$126k
American Heart Association 18POST34080005American Heart Association 19CSLOI34700047-lNHLBI NIH HHS F32 HL139046NHLBI NIH HHS K24 HL130553NHLBI NIH HHS UM1 HL087394NHLBI NIH HHS UM1 HL113456NIH HHS UM1 HL113456
6 · The paper itself

Abstract

Endogenous capability of the post-mitotic human heart holds great promise to restore the injured myocardium. Recent evidence indicates that the extracellular vesicles (EVs) regulate cardiac homeostasis and regeneration. Here, we investigated the molecular mechanism of EVs for self-repair. We isolated EVs from human iPSC-derived cardiomyocytes (iCMs), which were exposed to hypoxic (hEVs) and normoxic conditions (nEVs), and examined their roles in in vitro and in vivo models of cardiac injury. hEV treatment significantly improved the viability of hypoxic iCMs in vitro and cardiac function of severely injured murine myocardium in vivo. Microarray analysis of the EVs revealed significantly enriched expression of the miR-106a-363 cluster (miR cluster) in hEVs vs. nEVs. This miR cluster preserved survival and contractility of hypoxia-injured iCMs and maintained murine left-ventricular (LV) chamber size, improved LV ejection fraction, and reduced myocardial fibrosis of the injured myocardium. RNA-Seq analysis identified Jag1-Notch3-Hes1 as a target intracellular pathway of the miR cluster. Moreover, the study found that the cell cycle activator and cytokinesis genes were significantly up-regulated in the iCMs treated with miR cluster and Notch3 siRNA. Together, these results suggested that the miR cluster in the EVs stimulated cardiomyocyte cell cycle re-entry by repressing Notch3 to induce cell proliferation and augment myocardial self-repair. The miR cluster may represent an effective therapeutic approach for ischemic cardiomyopathy.

Indexed as

Cell ProliferationRegenerationAnimalsCell HypoxiaCell LineDisease Models, AnimalExtracellular VesiclesFemaleHumansInduced Pluripotent Stem CellsMaleMiceMice, Inbred C57BLMice, SCIDMicroRNAsMyocardial InfarctionMicroRNAsMIRN106 microRNA, humanNotch3 protein, mouseReceptor, Notch3Cell cycle re-entryEndogenous cardiac repair mechanismEVsIPSCsMiRNAsMyocardial Infarction

Identifiers

PMID33742276
PMCPMC8601755
OpenAlexW3137543695

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.