Evidence map›Paper›PMID 24899689›Full record

ArticleCirculation2014

Cardiac fibroblast glycogen synthase kinase-3β regulates ventricular remodeling and dysfunction in ischemic heart.

Hind Lal, Firdos Ahmad, Jibin Zhou, Justine E Yu, Ronald J Vagnozzi, Yuanjun Guo, Daohai Yu, Emily J Tsai, James Woodgett, Erhe Gao and 1 more

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

Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed
7.9field-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

119 citing papers in PubMed, 168 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Histone Deacetylase 6 Controls Atrial Fibrosis and Remodeling in Postinfarction Mice Through the Modulation of Wnt3a/GSK-3β Signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Antifibrotic effect of the P2X7 receptor antagonist A740003 against acute myocardial infarction-induced fibrotic remodelling.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024
    Article
  13. Article
  14. Article
  15. Fibroblasts under pressure: cardiac fibroblast responses to hypertension and antihypertensive therapies.American journal of physiology. Heart and circulatory physiology · 2024
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

59 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

11 authors at 2 institutions in 1 country.

Hind Lal *From the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Firdos Ahmad *From the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Jibin ZhouFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Justine E YuFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Ronald J VagnozziFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Yuanjun GuoFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Daohai YuFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Emily J TsaiFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
James WoodgettFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Erhe GaoFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.).
Thomas ForceFrom the Center for Translational Medicine (H.L., F.A., J.Z., J.E.U., R.J.V., Y.G., E.G., T.F.), Department of Clinical Sciences (D.Y.), and Section of Cardiology (E.J.T., T.F.), Temple University School of Medicine, Philadelphia, PA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (J.W.); and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (H.L., F.A., Y.G., T.F.). thomas.force@temple.edu Hind.lal@temple.edu.
Mount Sinai Hospital · CALunenfeld-Tanenbaum Research Institute · CA

Funding

Targeted Cancer Therapeutics and Heart Failure: Mechanisms and Post-injury RepairP01HL091799 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI KOCH, WALTER J. · 2008 to 2018
$23.1M
SIGNALING MECHANISMS GOVERNING CARDIAC HYPERTROPHYR01HL061688 · NHLBI · VANDERBILT UNIVERSITY · PI FORCE, THOMAS · 1999 to 2014
$5.7M
Signaling Mechanisms Governing Myocardial Fibrosis in Diseased HeartR01HL133290 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Hind Lal · 2017 to 2026
$3.6M
TNNI3K: A cardiac-specific kinase regulating ischemic injury and fibrotic remodelR01HL114124 · NHLBI · VANDERBILT UNIVERSITY · PI LAL, HIND · 2012 to 2015
$1.5M
Functional Implications of Caveolae-Localized Myocardial sGC in Heart FailureK08HL109159 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI TSAI, EMILY J · 2012 to 2016
$703k
CIHR FRN 12858NHLBI NIH HHS HL061688NHLBI NIH HHS HL091799NHLBI NIH HHS K08 HL109159NHLBI NIH HHS P01 HL091799NHLBI NIH HHS R01 HL061688NHLBI NIH HHS R01 HL114124NHLBI NIH HHS R01 HL133290
6 · The paper itself

Abstract

backgroundMyocardial infarction-induced remodeling includes chamber dilatation, contractile dysfunction, and fibrosis. Of these, fibrosis is the least understood. After myocardial infarction, activated cardiac fibroblasts deposit extracellular matrix. Current therapies to prevent fibrosis are inadequate, and new molecular targets are needed. METHODS AND

resultsHerein we report that glycogen synthase kinase-3β (GSK-3β) is phosphorylated (inhibited) in fibrotic tissues from ischemic human and mouse heart. Using 2 fibroblast-specific GSK-3β knockout mouse models, we show that deletion of GSK-3β in cardiac fibroblasts leads to fibrogenesis, left ventricular dysfunction, and excessive scarring in the ischemic heart. Deletion of GSK-3β induces a profibrotic myofibroblast phenotype in isolated cardiac fibroblasts, in post-myocardial infarction hearts, and in mouse embryonic fibroblasts deleted for GSK-3β. Mechanistically, GSK-3β inhibits profibrotic transforming growth factor-β1/SMAD-3 signaling via interactions with SMAD-3. Moreover, deletion of GSK-3β resulted in the significant increase of SMAD-3 transcriptional activity. This pathway is central to the pathology because a small-molecule inhibitor of SMAD-3 largely prevented fibrosis and limited left ventricular remodeling.

conclusionsThese studies support targeting GSK-3β in myocardial fibrotic disorders and establish critical roles of cardiac fibroblasts in remodeling and ventricular dysfunction.

Indexed as

AgedAnimalsEnzyme ActivationExtracellular MatrixFibroblastsFibrosisGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansMaleMice, KnockoutMiddle AgedMyocardial IschemiaMyocardiumPrimary Cell CultureRNA, Small InterferingGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanGsk3b protein, mouseRNA, Small InterferingSmad3 ProteinSmad3 protein, mousefibroblastsfibrosisglycogen synthase kinase 3 betahypertrophymyocardial infarction

Identifiers

PMID24899689
PMCPMC4153405
OpenAlexW2007412101

What OpenQuestion holds

Textmetadata
LicenceTDM
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.