Evidence map›Paper›PMID 24403517›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2014

20-HETE regulates the angiogenic functions of human endothelial progenitor cells and contributes to angiogenesis in vivo.

Li Chen, Rachel Ackerman, Mohamed Saleh, Katherine H Gotlinger, Michael Kessler, Lawrence G Mendelowitz, John R Falck, Ali S Arbab, A Guillermo Scicli, Michal L Schwartzman and 2 more

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

Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. The CYP/20-HETE/GPR75 axis in hypertension.Advances in pharmacology (San Diego, Calif.) · 2022
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Conflicting Roles of 20-HETE in Hypertension and Stroke.International journal of molecular sciences · 2019
    Review
  16. Therapeutic Ultrasound Increases Myocardial Blood Flow in Ischemic Myocardium and Cardiac Endothelial Cells: Results of In Vivo and In Vitro Experiments.Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography · 2019
    Article
  17. Article
  18. 20-HETE synthesis inhibition promotes cerebral protection after intracerebral hemorrhage without inhibiting angiogenesis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
    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

12 authors at 4 institutions in 2 countries.

Li ChenDepartment of Pharmacology, School of Medicine, Wuhan University, Wuhan, PR China (L.C., J.Y., A.M.G.); Department of Pharmacology, New York Medical College, Valhalla, New York (L.C., R.A.,M.S., K.H.G., M.L.S., A.M.G.); Department of Obstetrics and Gynecology, Westchester Medical Center, Valhalla, New York (M.K.); Obstetrics and Gynecology, Phelps Memorial Hospital Center, Sleepy Hollow, New York (L.G.M.); University of Texas Southwestern Medical Center, Dallas, Texas (J.R.F.); and Henry Ford Hospital, Detroit, Michigan (A.S.A., A.G.S.).
Rachel Ackerman
Mohamed Saleh
Katherine H Gotlinger
Michael Kessler
Lawrence G Mendelowitz
John R Falck
Ali S Arbab
A Guillermo Scicli
Michal L Schwartzman
Jing Yang
Austin M Guo
New York Medical College · USWuhan University · CNHenry Ford Hospital · USWestchester Medical Center · US

Funding

Vasoregulatory Function of CYP2E1-Derived EicosanoidsP01HL034300 · NHLBI · NEW YORK MEDICAL COLLEGE · PI JIANG, HOULI · 1985 to 2015
$33.4M
TRANSPORT EFFECTS OF ARACHIDONATE METABOLITES IN PERFUSED TUBULEP01DK038226 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BROWN, NANCY J. · 1986 to 2015
$22.1M
Understanding Mechanisms of Resistance to Anti-angiogenic TreatmentsR01CA160216 · NCI · HENRY FORD HEALTH SYSTEM · PI ARBAB, ALI SYED · 2012 to 2016
$1.8M
NCI NIH HHS 1R01-CA160216NCI NIH HHS R01 CA160216NHLBI NIH HHS HL34300NHLBI NIH HHS P01 HL034300NIDDK NIH HHS DK38226NIDDK NIH HHS P01 DK038226
6 · The paper itself

Abstract

Circulating endothelial progenitor cells (EPC) contribute to postnatal neovascularization. We identified the cytochrome P450 4A/F-20-hydroxyeicosatetraenoic acid (CYP4A/F-20-HETE) system as a novel regulator of EPC functions associated with angiogenesis in vitro. Here, we explored cellular mechanisms by which 20-HETE regulates EPC angiogenic functions and assessed its contribution to EPC-mediated angiogenesis in vivo. Results showed that both hypoxia and vascular endothelial growth factor (VEGF) induce CYP4A11 gene and protein expression (the predominant 20-HETE synthases in human EPC), and this is accompanied by an increase in 20-HETE production by ~1.4- and 1.8-fold, respectively, compared with the control levels. Additional studies demonstrated that 20-HETE and VEGF have a synergistic effect on EPC proliferation, whereas 20-HETE antagonist 20-HEDGE or VEGF-neutralizing antibody negated 20-HETE- or VEGF-induced proliferation, respectively. These findings are consistent with the presence of a positive feedback regulation on EPC proliferation between the 20-HETE and the VEGF pathways. Furthermore, we found that 20-HETE induced EPC adhesion to fibronectin and endothelial cell monolayer by 40 ± 5.6 and 67 ± 10%, respectively, which was accompanied by a rapid induction of very late antigen-4 and chemokine receptor type 4 mRNA and protein expression. Basal and 20-HETE-stimulated increases in adhesion were negated by the inhibition of the CYP4A-20-HETE system. Lastly, EPC increased angiogenesis in vivo by 3.6 ± 0.2-fold using the Matrigel plug angiogenesis assay, and these increases were markedly reduced by the local inhibition of 20-HETE system. These results strengthened the notion that 20-HETE regulates the angiogenic functions of EPC in vitro and EPC-mediated angiogenesis in vivo.

Indexed as

Neovascularization, PhysiologicAnimalsAntibodies, NeutralizingCell AdhesionCell HypoxiaCell ProliferationCytochrome P-450 CYP4ACytochrome P-450 Enzyme SystemEndothelium, VascularFeedback, PhysiologicalFemaleFibronectinsHumansHydroxyeicosatetraenoic AcidsIntegrin alpha4beta1Mice20-hydroxy-5,8,11,14-eicosatetraenoic acidAntibodies, NeutralizingCYP4A11 protein, humanCytochrome P-450 CYP4ACytochrome P-450 Enzyme SystemFibronectinsHydroxyeicosatetraenoic AcidsIntegrin alpha4beta1Receptors, CXCR4Vascular Endothelial Growth Factor A

Identifiers

PMID24403517
PMCPMC3935142
OpenAlexW1965222012

What OpenQuestion holds

Textmetadata
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.