Evidence map›Paper›PMID 25245104›Full record

ArticleCirculation research2014

Tbx5 is required for avian and Mammalian epicardial formation and coronary vasculogenesis.

Nata Y S-G Diman, Gabriel Brooks, Boudewijn P T Kruithof, Olivier Elemento, J G Seidman, Christine E Seidman, Craig T Basson, Cathy J Hatcher

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

Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
2.0field-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, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

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  14. Role of carotenoids and retinoids during heart development.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020
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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

8 authors at 1 institution in 1 country.

Nata Y S-G DimanFrom the Center for Molecular Cardiology, Greenberg Division of Cardiology (N.Y.S.-G.D., G.B., B.P.T.K., C.T.B., C.J.H.) and Department of Physiology and Biophysics (O.E.), Weill Cornell Medical College, New York, NY; Department of Genetics, Harvard Medical School, Boston, MA (J.G.S., C.E.S.); and Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, PA (C.J.H.).
Gabriel BrooksFrom the Center for Molecular Cardiology, Greenberg Division of Cardiology (N.Y.S.-G.D., G.B., B.P.T.K., C.T.B., C.J.H.) and Department of Physiology and Biophysics (O.E.), Weill Cornell Medical College, New York, NY; Department of Genetics, Harvard Medical School, Boston, MA (J.G.S., C.E.S.); and Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, PA (C.J.H.).
Boudewijn P T KruithofFrom the Center for Molecular Cardiology, Greenberg Division of Cardiology (N.Y.S.-G.D., G.B., B.P.T.K., C.T.B., C.J.H.) and Department of Physiology and Biophysics (O.E.), Weill Cornell Medical College, New York, NY; Department of Genetics, Harvard Medical School, Boston, MA (J.G.S., C.E.S.); and Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, PA (C.J.H.).
Olivier ElementoFrom the Center for Molecular Cardiology, Greenberg Division of Cardiology (N.Y.S.-G.D., G.B., B.P.T.K., C.T.B., C.J.H.) and Department of Physiology and Biophysics (O.E.), Weill Cornell Medical College, New York, NY; Department of Genetics, Harvard Medical School, Boston, MA (J.G.S., C.E.S.); and Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, PA (C.J.H.).
J G SeidmanFrom the Center for Molecular Cardiology, Greenberg Division of Cardiology (N.Y.S.-G.D., G.B., B.P.T.K., C.T.B., C.J.H.) and Department of Physiology and Biophysics (O.E.), Weill Cornell Medical College, New York, NY; Department of Genetics, Harvard Medical School, Boston, MA (J.G.S., C.E.S.); and Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, PA (C.J.H.).
Christine E SeidmanFrom the Center for Molecular Cardiology, Greenberg Division of Cardiology (N.Y.S.-G.D., G.B., B.P.T.K., C.T.B., C.J.H.) and Department of Physiology and Biophysics (O.E.), Weill Cornell Medical College, New York, NY; Department of Genetics, Harvard Medical School, Boston, MA (J.G.S., C.E.S.); and Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, PA (C.J.H.).
Craig T BassonFrom the Center for Molecular Cardiology, Greenberg Division of Cardiology (N.Y.S.-G.D., G.B., B.P.T.K., C.T.B., C.J.H.) and Department of Physiology and Biophysics (O.E.), Weill Cornell Medical College, New York, NY; Department of Genetics, Harvard Medical School, Boston, MA (J.G.S., C.E.S.); and Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, PA (C.J.H.). cathyha@pcom.edu craig.basson@novartis.com.
Cathy J HatcherFrom the Center for Molecular Cardiology, Greenberg Division of Cardiology (N.Y.S.-G.D., G.B., B.P.T.K., C.T.B., C.J.H.) and Department of Physiology and Biophysics (O.E.), Weill Cornell Medical College, New York, NY; Department of Genetics, Harvard Medical School, Boston, MA (J.G.S., C.E.S.); and Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, PA (C.J.H.). cathyha@pcom.edu craig.basson@novartis.com.
Harvard University · US

Funding

Mapping Transcriptional Networks in Cardiac DevelopmentU01HL098166 · NHLBI · HARVARD MEDICAL SCHOOL · PI SEIDMAN, JONATHAN G · 2009 to 2014
$9.5M
TBX5 and Coronary Blood Vessel DevelopmentR01HL080663 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI BASSON, CRAIG T · 2005 to 2008
$1.6M
Let-7 miRNA control of heart developmentRC1HL100579 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI HATCHER, CATHY J · 2009 to 2010
$997k
TBX5 and Histone Deacetylases in CardiogenesisK01HL080948 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI HATCHER, CATHY J · 2005 to 2009
$738k
NHLBI NIH HHS 5U01HL098166NHLBI NIH HHS K01 HL080948NHLBI NIH HHS R01 HL080663NHLBI NIH HHS R01 HL80663NHLBI NIH HHS RC1 HL100579NHLBI NIH HHS U01 HL098166
6 · The paper itself

Abstract

rationaleHolt-Oram syndrome is an autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. Overexpression of Tbx5 in the chick proepicardial organ impaired coronary blood vessel formation. However, the potential activity of Tbx5 in the epicardium itself, and the role of Tbx5 in mammalian coronary vasculogenesis, remains largely unknown.

objectiveTo evaluate the consequences of altered Tbx5 gene dosage during proepicardial organ and epicardial development in the embryonic chick and mouse. METHODS AND

resultsRetroviral-mediated knockdown or upregulation of Tbx5 expression in the embryonic chick proepicardial organ and proepicardial-specific deletion of Tbx5 in the embryonic mouse (Tbx5(epi-/)) impaired normal proepicardial organ cell development, inhibited epicardial and coronary blood vessel formation, and altered developmental gene expression. The generation of epicardial-derived cells and their migration into the myocardium were impaired between embryonic day (E) 13.5 to 15.5 in mutant hearts because of delayed epicardial attachment to the myocardium and subepicardial accumulation of epicardial-derived cells. This caused defective coronary vasculogenesis associated with impaired vascular smooth muscle cell recruitment and reduced invasion of cardiac fibroblasts and endothelial cells into myocardium. In contrast to wild-type hearts that exhibited an elaborate ventricular vascular network, Tbx5(epi-/-) hearts displayed a marked decrease in vascular density that was associated with myocardial hypoxia as exemplified by hypoxia inducible factor-1α upregulation and increased binding of hypoxyprobe-1. Tbx5(epi-/-) mice with such myocardial hypoxia exhibited reduced exercise capacity when compared with wild-type mice.

conclusionsOur findings support a conserved Tbx5 dose-dependent requirement for both proepicardial and epicardial progenitor cell development in chick and in mouse coronary vascular formation.

Indexed as

AnimalsCell MovementChick EmbryoCoronary VesselsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicOrganogenesisPericardiumSpecies SpecificityT-Box Domain ProteinsT-Box Domain ProteinsT-box transcription factor 5cell adhesioncell migrationcoronary vesselsepicardiummyocardiumTbx5transcription factors

Identifiers

PMID25245104
PMCPMC4727243
OpenAlexW2147691912

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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.