Evidence map›Paper›PMID 26586661›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Injury-Mediated Vascular Regeneration Requires Endothelial ER71/ETV2.

Changwon Park, Tae-Jin Lee, Suk Ho Bhang, Fang Liu, Rei Nakamura, Sunday S Oladipupo, Ian Pitha-Rowe, Benjamin Capoccia, Hong Seo Choi, Tae Min Kim and 9 more

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

44 citing papers in PubMed, 66 citations in OpenAlex.

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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

19 authors at 6 institutions in 3 countries.

Changwon Park *Department of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Tae-Jin Lee *Department of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Suk Ho BhangDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Fang LiuDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Rei NakamuraDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Sunday S OladipupoDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Ian Pitha-RoweDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Benjamin CapocciaDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Hong Seo ChoiDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Tae Min KimDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Norifumi UraoDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Masuko Ushio-FukaiDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Dong Jun LeeDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Hiroyuki MiyoshiDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Byung-Soo KimDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Dae-Sik LimDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Rajendra S ApteDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
David M OrnitzDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Kyunghee ChoiDepartment of Pediatrics (C.P., H.S.C.), Children's Heart Research and Outcomes Center (C.P.), Molecular and Systems Pharmacology Program (C.P.), Emory University School of Medicine, Atlanta; Department of Pharmacology, College of Medicine, University of Illinois at Chicago, IL (T.M.K., N.U., M.U-F.); School of Chemical Engineering, Sungkyunkwan University, Korea (S.H.B.); School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea (B-S.K.); Korea Advanced Institute of Science and Technology, Korea (D.J.L., D-S.L.); RIKEN BioResource Center, Japan (H.M.); the Departments of Pathology and Immunology (T-J.L., F.L., K.C.), Ophthalmology and Visual Sciences (R.N., I.P-R., R.S.A.), Developmental Biology (S.S.O., D.M.O.), Biochemistry and Molecular Biophysics (B. C.), Developmental, Regenerative, and Stem cell Biology Program (D.M.O., R.S.A., K.C.), Washington University School of Medicine, MO.
Korea Advanced Institute of Science and Technology · KRSungkyunkwan University · KRRIKEN BioResource Research Center · JPSeoul National University · KRUniversity of Illinois Chicago · USEmory University · US

Funding

WASHINGTON UNIVERSITY CENTER VISION RESEARCHP30EY002687 · NEI · WASHINGTON UNIVERSITY · PI Philip Andrew Ruzycki · 1985 to 2026
$18.4M
Hemangioglast Development and RegulationR01HL055337 · NHLBI · WASHINGTON UNIVERSITY · PI CHOI, KYUNGHEE · 2001 to 2024
$9.1M
CARDIOVASCULAR SYSTEM--FUNCTION/REGULATION/PHARMACOLOGYT32HL007275 · NHLBI · WASHINGTON UNIVERSITY · PI NERBONNE, JEANNE M. · 1985 to 2013
$6.0M
HEMATOPOIETIC COMMITMENT: MOLECULAR MECHANISMSR01HL063736 · NHLBI · WASHINGTON UNIVERSITY · PI CHOI, KYUNGHEE · 2000 to 2016
$5.6M
THE IMPORTANCE OF MACROPHAGE SENESCENCE IN REGULATING ANGIOGENESIS IN THE EYER01EY019287 · NEI · WASHINGTON UNIVERSITY · PI APTE, RAJENDRA S · 2010 to 2021
$3.9M
Mechanisms of ER71/ETV2-regulated VascularizationR01HL119291 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PARK, CHANGWON · 2013 to 2022
$3.2M
Copper transport protein and inflammatory angiogenesisR01HL116976 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FUKAI, TOHRU, USHIO-FUKAI, MASUKO · 2013 to 2016
$2.9M
FIBROBLAST GROWTH FACTOR SIGNALING IN HEART INJURY AND REPAIRR01HL105732 · NHLBI · WASHINGTON UNIVERSITY · PI ORNITZ, DAVID M · 2011 to 2015
$1.9M
Role of Cysteine Sulfenic Acid Formation in Compartmentalization of VEGF SignalinR21HL112293 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI USHIO-FUKAI, MASUKO · 2013 to 2014
$435k
HEMANGIOBLAST DEVELOPMENT AND REGULATIONR29HL055337 · NHLBI · WASHINGTON UNIVERSITY · PI CHOI, KYUNGHEE · 1996 to 2000
$94k
NEI NIH HHS NIH P30EY02687NEI NIH HHS NIH R01EY019287NEI NIH HHS P30 EY002687NEI NIH HHS R01 EY019287NHLBI NIH HHS HL105732NHLBI NIH HHS HL119291NHLBI NIH HHS HL55337NHLBI NIH HHS HL63736NHLBI NIH HHS NIH T32HL07275-34NHLBI NIH HHS R01 HL055337NHLBI NIH HHS R01 HL063736NHLBI NIH HHS R01 HL105732NHLBI NIH HHS R01 HL116976NHLBI NIH HHS R01 HL119291NHLBI NIH HHS R21 HL112293NHLBI NIH HHS R29 HL055337NHLBI NIH HHS T32 HL007275
6 · The paper itself

Abstract

objectiveComprehensive understanding of the mechanisms regulating angiogenesis might provide new strategies for angiogenic therapies for treating diverse physiological and pathological ischemic conditions. The E-twenty six (ETS) factor Ets variant 2 (ETV2; aka Ets-related protein 71) is essential for the formation of hematopoietic and vascular systems. Despite its indispensable function in vessel development, ETV2 role in adult angiogenesis has not yet been addressed. We have therefore investigated the role of ETV2 in vascular regeneration. APPROACH AND

resultsWe used endothelial Etv2 conditional knockout mice and ischemic injury models to assess the role of ETV2 in vascular regeneration. Although Etv2 expression was not detectable under steady-state conditions, its expression was readily observed in endothelial cells after injury. Mice lacking endothelial Etv2 displayed impaired neovascularization in response to eye injury, wounding, or hindlimb ischemic injury. Lentiviral Etv2 expression in ischemic hindlimbs led to improved recovery of blood perfusion with enhanced vessel formation. After injury, fetal liver kinase 1 (Flk1), aka VEGFR2, expression and neovascularization were significantly upregulated by Etv2, whereas Flk1 expression and vascular endothelial growth factor response were significantly blunted in Etv2-deficient endothelial cells. Conversely, enforced Etv2 expression enhanced vascular endothelial growth factor-mediated endothelial sprouting from embryoid bodies. Lentiviral Flk1 expression rescued angiogenesis defects in endothelial Etv2 conditional knockout mice after hindlimb ischemic injury. Furthermore, Etv2(+/-); Flk1(+/-) double heterozygous mice displayed a more severe hindlimb ischemic injury response compared with Etv2(+/-) or Flk1(+/-) heterozygous mice, revealing an epistatic interaction between ETV2 and FLK1 in vascular regeneration.

conclusionsOur study demonstrates a novel obligatory role for the ETV2 in postnatal vascular repair and regeneration.

Indexed as

Neovascularization, PhysiologicRegenerationAngiogenic ProteinsAnimalsCells, CulturedChoroidal NeovascularizationDisease Models, AnimalEndothelial CellsGene Expression RegulationGenetic VectorsGene Transfer TechniquesHeterozygoteHindlimbIschemiaLentivirusMaleAngiogenic ProteinsER71 protein, mouseTranscription FactorsVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVascular Endothelial Growth Factor Receptor-2endothelial cellshematopoietic systemshindlimb ischemiaregeneration

Identifiers

PMID26586661
PMCPMC4690812
OpenAlexW2253553499

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