Evidence map›Paper›PMID 37534464›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2023

Flk1 Deficiency and Hypoxia Synergistically Promote Endothelial Dysfunction, Vascular Remodeling, and Pulmonary Hypertension.

Tatsuya Akiyama, Taketaro Sadahiro, Yu Yamada, Ryo Fujita, Yuto Abe, Koji Nakano, Seiichiro Honda, Masatsugu Ema, Yoshiaki Kubota, Satoshi Sakai and 2 more

Open access · bronzeAbstract read
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In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.1field-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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Ambient PMEnvironment & health (Washington, D.C.) · 2026
    Article
  2. Review
  3. The emerging role of integrin signaling in pulmonary vascular disease.American journal of physiology. Lung cellular and molecular physiology · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Tatsuya Akiyama *Department of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Taketaro Sadahiro *Department of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.ORCID 0000-0002-9341-4506
Yu YamadaDepartment of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.ORCID 0000-0003-0113-1785
Ryo FujitaDepartment of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.ORCID 0000-0002-8392-0122
Yuto AbeDepartment of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.ORCID 0009-0002-6009-1074
Koji NakanoDepartment of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Seiichiro HondaDepartment of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.ORCID 0009-0005-8928-8884
Masatsugu EmaDivision of Regenerative Medicine, Transborder Medical Research Center (R.F.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Yoshiaki KubotaDepartments of Anatomy (Y.K.), Keio University School of Medicine, Tokyo, Japan.ORCID 0000-0001-6672-4122
Satoshi SakaiDepartment of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.ORCID 0000-0001-9599-7349
Nobuyuki HizawaDepartment of Respiratory Medicine (T.A., N.H.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Masaki IedaDepartment of Cardiology (T.A., T.S., Y.Y., R.F., Y.A., K.N., S.H., S.S., M.I.), Institute of Medicine, University of Tsukuba, Ibaraki, Japan.ORCID 0000-0003-4724-3299
University of Tsukuba · JPInstitute of Applied Biochemistry · JPKeio University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe mechanisms underlying pulmonary hypertension (PH) remain largely unknown; further, why advanced vascular remodeling preferentially occurs in arterioles is yet to be answered. VEGF (vascular endothelial growth factor) regulates angiogenesis through Flk1 (fetal liver kinase 1) and Flt1 (fms-like tyrosine kinase 1) on endothelial cells (ECs), which may be related to PH pathogenesis. However, spatiotemporal expression patterns of Flk1 and Flt1 in the pulmonary vascular system and the role of endothelial Flk1 in PH development remain poorly understood.

methodsWe analyzed multiple reporter mice, including Flk1-GFP (green fluorescent protein) bacterial artificial chromosome transgenic (Tg), Flt1-DsRed bacterial artificial chromosome Tg, and Flk1-GFP/Flt1-DsRed double Tg mice, to determine the spatiotemporal expression of Flk1 and Flt1 in hypoxia-induced PH. We also used Cdh5

resultsFlk1 was specifically expressed in the ECs of small pulmonary vessels, including arterioles. Conversely, Flt1 was more broadly expressed in the ECs of large- to small-sized vessels in adult mouse lungs. Intriguingly, Flk1

conclusionsFlk1 and Flt1 were differentially expressed in pulmonary ECs. Flk1 deficiency and hypoxia jointly dysregulated arteriolar ECs to promote vascular remodeling. Thus, dysfunction of Flk1

Indexed as

Hypertension, PulmonaryVascular RemodelingAnimalsEndothelial CellsGreen Fluorescent ProteinsHypoxiaMiceMice, KnockoutMice, TransgenicVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Green Fluorescent ProteinsKdr protein, mouseVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2endothelial cellshypertensionhypoxiapulmonaryvascular endothelial growth factor Avascular remodeling

Identifiers

PMID37534464
OpenAlexW4385514563

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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.