Evidence map›Paper›PMID 27288437›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2016

Carvedilol-responsive microRNAs, miR-199a-3p and -214 protect cardiomyocytes from simulated ischemia-reperfusion injury.

Kyoung-Mi Park, Jian-Peng Teoh, Yongchao Wang, Zuzana Broskova, Ahmed S Bayoumi, Yaoliang Tang, Huabo Su, Neal L Weintraub, Il-Man Kim

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

Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.

  1. Guidelines for experimental models of myocardial ischemia and infarction.American journal of physiology. Heart and circulatory physiology · 2018
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  13. MiR-199a-3p promotes repair of myocardial infarction by targeting NACC2.International journal of clinical and experimental pathology · 2023
    Article
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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

9 authors at 1 institution in 1 country.

Kyoung-Mi ParkVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia;
Jian-Peng TeohVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia;
Yongchao WangVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia;
Zuzana BroskovaVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia;
Ahmed S BayoumiVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia;
Yaoliang TangVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia;
Huabo SuVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia; Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia;
Neal L WeintraubVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia;
Il-Man KimVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia ilkim@augusta.edu.
Augusta University · US

Funding

Neddylation and cardiac protein quality controlR01HL124248 · NHLBI · AUGUSTA UNIVERSITY · PI SU, HUABO · 2014 to 2024
$4.1M
Notch1/miR-322 Axis in Stem Cell Mediated Vascular RepairR01HL134354 · NHLBI · AUGUSTA UNIVERSITY · PI ASHRAF, MUHAMMAD, TANG, YAO LIANG · 2016 to 2020
$2.5M
Beta-arrestin signaling and microRNA biogenesis in cardioprotectionR01HL124251 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI KIM, IL-MAN · 2014 to 2018
$1.9M
Epigenetic regulation of HDAC9 in obesity and atherosclerosisR01HL126949 · NHLBI · AUGUSTA UNIVERSITY · PI WEINTRAUB, NEAL L · 2016 to 2019
$1.8M
American Heart Association-American Stroke Association 14SDG18970040NHLBI NIH HHS R01 HL124248NHLBI NIH HHS R01 HL124251NHLBI NIH HHS R01 HL126949NHLBI NIH HHS R01 HL134354
6 · The paper itself

Abstract

The nonselective β-adrenergic receptor antagonist (β-blocker) carvedilol has been shown to protect against myocardial injury, but the detailed underlying mechanisms are unclear. We recently reported that carvedilol stimulates the processing of microRNA (miR)-199a-3p and miR-214 in the heart via β-arrestin1-biased β1-adrenergic receptor (β1AR) cardioprotective signaling. Here, we investigate whether these β-arrestin1/β1AR-responsive miRs mediate the beneficial effects of carvedilol against simulated ischemia/reperfusion (sI/R). Using cultured cardiomyocyte cell lines and primary cardiomyocytes, we demonstrate that carvedilol upregulates miR-199a-3p and miR-214 in both ventricular and atrial cardiomyocytes subjected to sI/R. Overexpression of the two miRs in cardiomyocytes mimics the effects of carvedilol to activate p-AKT survival signaling and the expression of a downstream pluripotency marker Sox2 in response to sI/R. Moreover, carvedilol-mediated p-AKT activation is abolished by knockdown of either miR-199a-3p or miR-214. Along with previous studies to directly link the cardioprotective actions of carvedilol to upregulation of p-AKT/stem cell markers, our findings suggest that the protective roles of carvedilol during ischemic injury are in part attributed to activation of these two protective miRs. Loss of function of miR-199a-3p and miR-214 also increases cardiomyocyte apoptosis after sI/R. Mechanistically, we demonstrate that miR-199a-3p and miR-214 repress the predictive or known apoptotic target genes ddit4 and ing4, respectively, in cardiomyocytes. These findings suggest pivotal roles for miR-199a-3p and miR-214 as regulators of cardiomyocyte survival and contributors to the functional benefits of carvedilol therapy.

Indexed as

Adrenergic beta-AntagonistsAnimalsApoptosisCarbazolesCarvedilolCell LineCells, CulturedComputer SimulationImmunoblottingIn Situ Nick-End LabelingIn Vitro TechniquesMiceMice, Inbred C57BLMicroRNAsMyocytes, CardiacPropanolaminesAdrenergic beta-AntagonistsCarbazolesCarvedilolMicroRNAsMirn199 microRNA, mouseMIRN199 microRNA, ratMirn214 microRNA, mouseMirn214 microRNA, ratPropanolaminesapoptosisheart diseasemicroRNAsβ-arrestin-biased β-adrenergic receptor signalingβ-blocker

Identifiers

PMID27288437
PMCPMC5005281
OpenAlexW2413893340

What OpenQuestion holds

Textmetadata
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.