Evidence map›Paper›PMID 24622244›Full record

ArticleCirculation. Heart failure2014

Novel protective role of endogenous cardiac myocyte P2X4 receptors in heart failure.

Tiehong Yang, Jian-bing Shen, Ronghua Yang, John Redden, Kimberly Dodge-Kafka, James Grady, Kenneth A Jacobson, Bruce T Liang

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

Article in Circulation. Heart failure, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.5field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 35 citations in OpenAlex.

  1. MRS2339, a cardiac P2X4 receptor nucleotide activator, improves systolic function in heart failure.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
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  10. P2X4 receptor exacerbates ischemic AKI and induces renal proximal tubular NLRP3 inflammasome signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
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  13. CaJournal of cardiovascular development and disease · 2019
    Review
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  20. P2X4 Receptor Reporter Mice: Sparse Brain Expression and Feeding-Related Presynaptic Facilitation in the Arcuate Nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016
    Article
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

8 authors at 1 institution in 1 country.

Tiehong YangFrom Pat and Jim Calhoun Cardiology Center, University of Connecticut Medical Center, Farmington, CT (T.Y., J.S., R.Y., J.R., K.D.-K., J.G., B.T.L.); and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (K.A.J.).
Jian-bing ShenFrom Pat and Jim Calhoun Cardiology Center, University of Connecticut Medical Center, Farmington, CT (T.Y., J.S., R.Y., J.R., K.D.-K., J.G., B.T.L.); and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (K.A.J.).
Ronghua YangFrom Pat and Jim Calhoun Cardiology Center, University of Connecticut Medical Center, Farmington, CT (T.Y., J.S., R.Y., J.R., K.D.-K., J.G., B.T.L.); and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (K.A.J.).
John ReddenFrom Pat and Jim Calhoun Cardiology Center, University of Connecticut Medical Center, Farmington, CT (T.Y., J.S., R.Y., J.R., K.D.-K., J.G., B.T.L.); and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (K.A.J.).
Kimberly Dodge-KafkaFrom Pat and Jim Calhoun Cardiology Center, University of Connecticut Medical Center, Farmington, CT (T.Y., J.S., R.Y., J.R., K.D.-K., J.G., B.T.L.); and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (K.A.J.).
James GradyFrom Pat and Jim Calhoun Cardiology Center, University of Connecticut Medical Center, Farmington, CT (T.Y., J.S., R.Y., J.R., K.D.-K., J.G., B.T.L.); and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (K.A.J.).
Kenneth A JacobsonFrom Pat and Jim Calhoun Cardiology Center, University of Connecticut Medical Center, Farmington, CT (T.Y., J.S., R.Y., J.R., K.D.-K., J.G., B.T.L.); and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (K.A.J.).
Bruce T LiangFrom Pat and Jim Calhoun Cardiology Center, University of Connecticut Medical Center, Farmington, CT (T.Y., J.S., R.Y., J.R., K.D.-K., J.G., B.T.L.); and Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (K.A.J.). bliang@uchc.edu.
National Institutes of Health · US

Funding

Development of Drugs Acting at Ion ChannelsZIADK031127 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI JACOBSON, KENNETH ALAN · 2009 to 2025
$3.9M
PURINERGIC SIGNALING IN CULTURED HEART CELLSR01HL048225 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LIANG, BRUCE T · 1993 to 2005
$1.9M
Intramural NIH HHS Z99 DK999999Intramural NIH HHS ZIA DK031127NHLBI NIH HHS HL48225NHLBI NIH HHS R01 HL048225
6 · The paper itself

Abstract

backgroundHeart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. METHODS AND

resultsMice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation-induced postinfarct or transverse aorta constriction-induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N(5)-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout.

conclusionsThis study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection.

Indexed as

AnimalsCoronary VesselsDisease Models, AnimalFemaleHeart FailureLigationMaleMiceMice, KnockoutMice, TransgenicMyocardial InfarctionMyocytes, CardiacNitric Oxide Synthase Type IIIReceptors, Purinergic P2X4Nitric Oxide Synthase Type IIIReceptors, Purinergic P2X4heart failuremyocytes, cardiacpurines

Identifiers

PMID24622244
PMCPMC4289151
OpenAlexW2160864523

What OpenQuestion holds

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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.