Evidence map›Paper›PMID 25116956›Full record

ArticleCirculation2014

Alternatively spliced tissue factor promotes plaque angiogenesis through the activation of hypoxia-inducible factor-1α and vascular endothelial growth factor signaling.

Chiara Giannarelli, Matilde Alique, David T Rodriguez, Dong Kwon Yang, Dongtak Jeong, Claudia Calcagno, Randolph Hutter, Antoine Millon, Jason C Kovacic, Thomas Weber and 6 more

RetractedErratum issuedAbstract 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. It has been retracted, and should not be counted. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

35 citing papers in PubMed, 49 citations in OpenAlex.

  1. Curcumin Protected CoClFood science & nutrition · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Chiara GiannarelliFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.). chiara.giannarelli@mssm.edu.
Matilde AliqueFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
David T RodriguezFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Dong Kwon YangFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Dongtak JeongFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Claudia CalcagnoFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Randolph HutterFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Antoine MillonFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Jason C KovacicFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Thomas WeberFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Peter L FariesFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Gerald A SoffFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Zahi A FayadFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Roger J HajjarFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Valentin FusterFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Juan J BadimonFrom the AtheroThrombosis Research Unit (C.G., M.A., D.T.R., J.J.B.), Cardiovascular Research Institute (C.G., D.K.Y., D.J., J.C.K., T.W., R.J.H., V.F.), Translational and Molecular Imaging Institute (C.C., A.M., Z.A.F.), Department of Radiology (C.C., A.M., Z.A.F.), and Vascular Surgery (P.L.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Memorial Sloan-Kettering, New York, NY (G.A.S.); and CNIC, Madrid, Spain (V.F.).
Spanish National Centre for Cardiovascular Research · ESAnna Needs Neuroblastoma Answers · USMemorial Sloan Kettering Cancer Center · US

Funding

TRAINING PROGRAM IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007824 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GELB, BRUCE D · 1995 to 2022
$8.6M
MR/PET Imaging of coronary atherosclerosisR01HL071021 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI FAYAD, ZAHI A. · 2002 to 2019
$7.8M
Gene Therapy with Cardiotropic Vectors for the Treatment of Heart FailureR01HL088434 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2010 to 2013
$1.7M
Regression of cardiac hypertrophyR01HL093183 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J. · 2009 to 2010
$1.1M
Role of alternatively spliced Tissue Factor in atherosclerosisK23HL111339 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GIANNARELLI, CHIARA · 2013 to 2017
$782k
Cellular and molecular mechanisms of endothelial repair and atherosclerosisK08HL111330 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVACIC, JASON CIRIL · 2012 to 2016
$647k
NHLBI NIH HHS 5T32HL7824-15NHLBI NIH HHS HL088434NHLBI NIH HHS K08 HL111330NHLBI NIH HHS K08HL111330NHLBI NIH HHS K23 HL111339NHLBI NIH HHS K23HL111339NHLBI NIH HHS R01 HL071021NHLBI NIH HHS R01HL071021NHLBI NIH HHS R01 HL088434NHLBI NIH HHS R01 HL093183NHLBI NIH HHS T32 HL007824
6 · The paper itself

Abstract

backgroundAlternatively spliced tissue factor (asTF) is a novel isoform of full-length tissue factor, which exhibits angiogenic activity. Although asTF has been detected in human plaques, it is unknown whether its expression in atherosclerosis causes increased neovascularization and an advanced plaque phenotype. METHODS AND

resultsCarotid (n=10) and coronary (n=8) specimens from patients with stable or unstable angina were classified as complicated or uncomplicated on the basis of plaque morphology. Analysis of asTF expression and cell type-specific expression revealed a strong expression and colocalization of asTF with macrophages and neovessels within complicated, but not uncomplicated, human plaques. Our results showed that the angiogenic activity of asTF is mediated via hypoxia-inducible factor-1α upregulation through integrins and activation of phosphatidylinositol-3-kinase/Akt and mitogen-activated protein kinase pathways. Hypoxia-inducible factor-1α upregulation by asTF also was associated with increased vascular endothelial growth factor expression in primary human endothelial cells, and vascular endothelial growth factor-Trap significantly reduced the angiogenic effect of asTF in vivo. Furthermore, asTF gene transfer significantly increased neointima formation and neovascularization after carotid wire injury in ApoE(-/-) mice.

conclusionsThe results of this study provide strong evidence that asTF promotes neointima formation and angiogenesis in an experimental model of accelerated atherosclerosis. Here, we demonstrate that the angiogenic effect of asTF is mediated via the activation of the hypoxia-inducible factor-1/vascular endothelial growth factor signaling. This mechanism may be relevant to neovascularization and the progression and associated complications of human atherosclerosis as suggested by the increased expression of asTF in complicated versus uncomplicated human carotid and coronary plaques.

Indexed as

Alternative SplicingAnimalsApolipoproteins ECarotid ArteriesCoronary VesselsDisease Models, AnimalEndothelium, VascularHumansHypoxia-Inducible Factor 1, alpha SubunitMaleMiceMice, Inbred C57BLNeointimaNeovascularization, PathologicPlaque, AtheroscleroticSignal TransductionApolipoproteins EHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitThromboplastinVascular Endothelial Growth Factor Aalternative splicingatherosclerosishypoxia-inducible factor 1neovascularization, physiologic procoagulant, tissue factorthromboplastinvascular endothelial growth factors

Identifiers

PMID25116956
PMCPMC4190117
OpenAlexW2128529999

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Read underepoch 390

Registered trials

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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.