Evidence map›Paper›PMID 24695532›Full record

ArticlePloS one2014

Apelin increases cardiac contractility via protein kinase Cε- and extracellular signal-regulated kinase-dependent mechanisms.

Ábel Perjés, Réka Skoumal, Olli Tenhunen, Attila Kónyi, Mihály Simon, Iván G Horváth, Risto Kerkelä, Heikki Ruskoaho, István Szokodi

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
8.6field-weighted citation impact, top 2% 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

54 citing papers in PubMed, 92 citations in OpenAlex.

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  12. Adipokines and Their Role in Heart Failure: A Literature Review.The Journal of innovations in cardiac rhythm management · 2023
    Review
  13. Review
  14. Apelin as a Potential Regulator of Peak Athletic Performance.International journal of molecular sciences · 2023
    Article
  15. Review
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  19. Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021
    Review
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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 4 institutions in 2 countries.

Ábel PerjésDepartment of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Oulu, Finland; Heart Institute, Medical School, University of Pécs, Pécs, Hungary; Szentágothai Research Center, University of Pécs, Pécs, Hungary.
Réka SkoumalHeart Institute, Medical School, University of Pécs, Pécs, Hungary; Szentágothai Research Center, University of Pécs, Pécs, Hungary.
Olli TenhunenDepartment of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Oulu, Finland.
Attila KónyiHeart Institute, Medical School, University of Pécs, Pécs, Hungary; Szentágothai Research Center, University of Pécs, Pécs, Hungary.
Mihály SimonHeart Institute, Medical School, University of Pécs, Pécs, Hungary; Szentágothai Research Center, University of Pécs, Pécs, Hungary.
Iván G HorváthHeart Institute, Medical School, University of Pécs, Pécs, Hungary; Szentágothai Research Center, University of Pécs, Pécs, Hungary.
Risto KerkeläDepartment of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu, Finland.
Heikki RuskoahoDepartment of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Oulu, Finland; Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
István SzokodiHeart Institute, Medical School, University of Pécs, Pécs, Hungary; Szentágothai Research Center, University of Pécs, Pécs, Hungary.
University of Pecs · HUUniversity of Oulu · FIOulu University Hospital · FIUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundApelin, the endogenous ligand for the G protein-coupled apelin receptor, is an important regulator of the cardiovascular homoeostasis. We previously demonstrated that apelin is one of the most potent endogenous stimulators of cardiac contractility; however, its underlying signaling mechanisms remain largely elusive. In this study we characterized the contribution of protein kinase C (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2) and myosin light chain kinase (MLCK) to the positive inotropic effect of apelin. METHODS AND

resultsIn isolated perfused rat hearts, apelin increased contractility in association with activation of prosurvival kinases PKC and ERK1/2. Apelin induced a transient increase in the translocation of PKCε, but not PKCα, from the cytosol to the particulate fraction, and a sustained increase in the phosphorylation of ERK1/2 in the left ventricle. Suppression of ERK1/2 activation diminished the apelin-induced increase in contractility. Although pharmacological inhibition of PKC attenuated the inotropic response to apelin, it had no effect on ERK1/2 phosphorylation. Moreover, the apelin-induced positive inotropic effect was significantly decreased by inhibition of MLCK, a kinase that increases myofilament Ca2+ sensitivity.

conclusionsApelin increases cardiac contractility through parallel and independent activation of PKCε and ERK1/2 signaling in the adult rat heart. Additionally MLCK activation represents a downstream mechanism in apelin signaling. Our data suggest that, in addition to their role in cytoprotection, modest activation of PKCε and ERK1/2 signaling improve contractile function, therefore these pathways represent attractive possible targets in the treatment of heart failure.

Indexed as

AnimalsApelinHeart VentriclesIntercellular Signaling Peptides and ProteinsMaleMAP Kinase Signaling SystemMuscle ContractionMyocardial ContractionMyosin-Light-Chain KinasePhosphorylationProtein Kinase C-alphaProtein Kinase C-epsilonRatsRats, Sprague-DawleySignal TransductionApelinApln protein, ratIntercellular Signaling Peptides and ProteinsMyosin-Light-Chain KinaseProtein Kinase C-alphaProtein Kinase C-epsilon

Identifiers

PMID24695532
PMCPMC3973555
OpenAlexW2022701671

What OpenQuestion holds

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LicenceCC BY
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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.