Evidence map›Paper›PMID 22354898›Full record

ArticleCardiovascular research2012

Loss of the miR-144/451 cluster impairs ischaemic preconditioning-mediated cardioprotection by targeting Rac-1.

Xiaohong Wang, Hongyan Zhu, Xiaowei Zhang, Yong Liu, Jing Chen, Mario Medvedovic, Hongliang Li, Mitchell J Weiss, Xiaoping Ren, Guo-Chang Fan

Abstract read
In one paragraph

Article in Cardiovascular research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

75 citing papers in PubMed, 1 synthesis or guideline pooled it.

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15 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

10 authors.

Xiaohong WangDepartment of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, USA.
Hongyan Zhu
Xiaowei Zhang
Yong Liu
Jing Chen
Mario Medvedovic
Hongliang Li
Mitchell J Weiss
Xiaoping Ren
Guo-Chang Fan

Funding

Cincinnati Center for Clinical and Translational Sciences and TrainingUL1TR000077 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., TSEVAT, JOEL · 2012 to 2014
$9.9M
Roles of Hsp20-Exosomes in Myocardial AngiogenesisR01HL087861 · NHLBI · UNIVERSITY OF CINCINNATI · PI FAN, GUO-CHANG · 2007 to 2017
$4.2M
Regulation of erythropoiesis by the miR-144/451 microRNA locusR01DK092318 · NIDDK · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI WEISS, MITCHELL J · 2012 to 2016
$1.8M
NCATS NIH HHS UL1 TR000077NHLBI NIH HHS HL-087861NHLBI NIH HHS R01 HL087861NIDDK NIH HHS R01 DK092318
6 · The paper itself

Abstract

aimsWhile a wealth of data has uncovered distinct microRNA (miR) expression alterations in hypertrophic and ischaemic/reperfused (I/R) hearts, little is known about miR regulation and response to ischaemic preconditioning (IPC). METHODS AND

resultsWe analysed miRs in murine hearts preconditioned with six cycles of 4 min ischaemia via coronary artery occlusion, followed by 4 min reperfusion in vivo. Both miRs within the miR-144/451 cluster were the most elevated among a cohort of 21 dysregulated miRs in preconditioned hearts, compared with shams. To investigate the significance of this finding, we examined IPC-mediated cardioprotection within a miR-144/451-knockout (KO) mouse model. Wild-type (WT) hearts exposed to IPC followed by I/R (30 min/24 h) showed a smaller infarction size compared with mice treated with I/R alone. In contrast, IPC failed to protect miR-144/451-KO hearts against infarct caused by I/R treatment. Thus, the miR-144/451 cluster is required for IPC-elicited cardioprotection. Rac-1, a key component of NADPH oxidase, was mostly up-regulated in KO hearts among three bona fide targets (Rac-1, 14-3-3ζ, and CUGBP2) for both miR-144 and miR-451. Accordingly, reactive oxygen species (ROS) levels were markedly increased in KO hearts upon IPC, compared with IPC-WT hearts. Pre-treatment of KO hearts with a Rac-1 inhibitor NSC23766 (20 mg/kg, ip) reduced IPC-triggered ROS levels and restored IPC-elicited cardioprotection. Using antagomiRs, we showed that miR-451 was largely responsible for IPC-mediated cardioprotection.

conclusionLoss of the miR-144/451 cluster limits IPC cardioprotection by up-regulating Rac-1-mediated oxidative stress signalling.

Indexed as

AnimalsBlotting, WesternIschemic Preconditioning, MyocardialMiceMice, KnockoutMicroRNAsMyocardial InfarctionMyocardial Reperfusion InjuryMyocardiumOxidative StressReactive Oxygen SpeciesMicroRNAsMIRN144 microRNA, mouseMirn451 microRNA, mouseReactive Oxygen Species

Identifiers

PMID22354898
PMCPMC3331614

What OpenQuestion holds

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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.