Evidence map›Paper›PMID 24727028›Full record

ArticleCirculation research2014

Fli1 acts downstream of Etv2 to govern cell survival and vascular homeostasis via positive autoregulation.

Md J Abedin, Annie Nguyen, Nan Jiang, Cameron E Perry, John M Shelton, Dennis K Watson, Anwarul Ferdous

Open access · bronzeAbstract 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 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

36 citing papers in PubMed, 43 citations in OpenAlex.

  1. Molecular Mechanisms Governing Vascular Function in Heart Failure.Arteriosclerosis, thrombosis, and vascular biology · 2026
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  4. Endothelial to mesenchymal transition: a central mechanism in diabetes-induced vascular pathology.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
    Review
  5. Article
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  9. Ang-1 and VEGF: central regulators of angiogenesis.Molecular and cellular biochemistry · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Endothelial Cell Differentiation and Hemogenic Specification.Cold Spring Harbor perspectives in medicine · 2022
    Review
  17. Article
  18. Hemogenic and aortic endothelium arise from a common hemogenic angioblast precursor and are specified by the Etv2 dosage.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  19. Article
  20. 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

7 authors at 2 institutions in 1 country.

Md J AbedinFrom the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.).
Annie NguyenFrom the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.).
Nan JiangFrom the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.).
Cameron E PerryFrom the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.).
John M SheltonFrom the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.).
Dennis K WatsonFrom the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.).
Anwarul FerdousFrom the Department of Internal Medicine (Cardiology) (M.J.A., A.N., N.J., C.E.P., J.M.S., A.F.), University of Texas Southwestern Medical Center, Dallas; Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston (D.K.W.); and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis (M.J.A.). anwarul.ferdous@utsouthwestern.edu.
MUSC Hollings Cancer Center · USMedical University of South Carolina · US

Funding

Functional Genomics of Complex Vascular DiseaseP30HL101254 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2009 to 2010
$1.3M
NHLBI NIH HHS P30 HL101254NHLBI NIH HHS P30-HL101254-01
6 · The paper itself

Abstract

rationaleCardiovascular health depends on proper development and integrity of blood vessels. Ets variant 2 (Etv2), a member of the E26 transforming-specific family of transcription factors, is essential to initiate a transcriptional program leading to vascular morphogenesis in early mouse embryos. However, endothelial expression of the Etv2 gene ceases at midgestation; therefore, vascular development past this stage must continue independent of Etv2.

objectiveTo identify molecular mechanisms underlying transcriptional regulation of vascular morphogenesis and homeostasis in the absence of Etv2. METHODS AND

resultsUsing loss- and gain-of-function strategies and a series of molecular techniques, we identify Friend leukemia integration 1 (Fli1), another E26 transforming-specific family transcription factor, as a downstream target of Etv2. We demonstrate that Etv2 binds to conserved Ets-binding sites within the promoter region of the Fli1 gene and governs Fli1 expression. Importantly, in the absence of Etv2 at midgestation, binding of Etv2 at Ets-binding sites in the Fli1 promoter is replaced by Fli1 protein itself, sustaining expression of Fli1 as well as selective Etv2-regulated endothelial genes to promote endothelial cell survival and vascular integrity. Consistent with this, we report that Fli1 binds to the conserved Ets-binding sites within promoter and enhancer regions of other Etv2-regulated endothelial genes, including Tie2, to control their expression at and beyond midgestation.

conclusionsWe have identified a novel positive feed-forward regulatory loop in which Etv2 activates expression of genes involved in vasculogenesis, including Fli1. Once the program is activated in early embryos, Fli1 then takes over to sustain the process in the absence of Etv2.

Indexed as

AnimalsCell SurvivalEmbryonic DevelopmentEndothelium, VascularFemaleHemorrhageHomeostasisMaleMiceMice, KnockoutMice, TransgenicModels, AnimalMorphogenesisNeovascularization, PhysiologicProto-Oncogene Protein c-fli-1Transcription FactorsER71 protein, mouseFli1 protein, mouseProto-Oncogene Protein c-fli-1Transcription Factorsapoptosisdevelopmental biologyembryonic developmentgene expressionhomeostasistranscription factors

Identifiers

PMID24727028
PMCPMC4080722
OpenAlexW2129206121

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.