Evidence map›Paper›PMID 27222313›Full record

ArticleJournal of cellular and molecular medicine2016

Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia.

Lili Zhang, Xiangru Lu, Le Gui, Yan Wu, Stephen M Sims, Guoping Wang, Qingping Feng

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

Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 26% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

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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

7 authors at 5 institutions in 2 countries.

Lili ZhangInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiangru LuDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Le GuiDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Yan WuDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Stephen M SimsDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Guoping WangInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qingping FengDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Huazhong University of Science and Technology · CNWestern University · CACentral South University · CNLawson Health Research Institute · CANantong University · CN

Funding

CIHR MOP‐64453
6 · The paper itself

Abstract

Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload-induced Ca(2+) release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd) ) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1(f/f) mice. Remarkably, I/R-induced ventricular arrhythmia was significantly decreased in Rac1(ckd) compared to Rac1(f/f) mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R-induced ventricular arrhythmia. Ca(2+) imaging analysis showed that in response to a 6 mM external Ca(2+) concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca(2+) waves in Rac1(f/f) cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R-induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1(ckd) mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease.

Indexed as

AnimalsArrhythmias, CardiacCalciumElectrocardiographyGene Knockdown TechniquesHeart RateHeart VentriclesMice, Inbred C57BLMyocardial ReperfusionMyocytes, CardiacOxidation-Reductionrac1 GTP-Binding ProteinRyanodine Receptor Calcium Release ChannelSuperoxidesCalciumrac1 GTP-Binding ProteinRyanodine Receptor Calcium Release ChannelSuperoxidesarrhythmiaischaemia and reperfusionRac1reactive oxygen speciesstore overload-induced calcium release

Identifiers

PMID27222313
PMCPMC4956946
OpenAlexW2399528279

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.