Evidence map›Paper›PMID 18945963›Full record

ArticleBlood2009

Placenta growth factor induces 5-lipoxygenase-activating protein to increase leukotriene formation in sickle cell disease.

Nitin Patel, Caryn S Gonsalves, Minyang Yang, Punam Malik, Vijay K Kalra

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed, 45 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Crosstalk Between Sickle Cell Disease and Ferroptosis.International journal of molecular sciences · 2025
    Review
  4. Ferroptosis as an emerging target in sickle cell disease.Current research in toxicology · 2024
    Article
  5. Review
  6. Review
  7. Airway Inflammation and Lung Function in Sickle Cell Disease.Pediatric allergy, immunology, and pulmonology · 2019
    Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Inflammatory targets of therapy in sickle cell disease.Translational research : the journal of laboratory and clinical medicine · 2016
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. PlGF: a multitasking cytokine with disease-restricted activity.Cold Spring Harbor perspectives in medicine · 2012
    Review
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

5 authors at 2 institutions in 1 country.

Nitin PatelDepartment of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Caryn S Gonsalves
Minyang Yang
Punam Malik
Vijay K Kalra
University of Southern California · USCincinnati Children's Hospital Medical Center · US

Funding

USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KAPLOWITZ, NEIL · 1995 to 2020
$21.8M
ROLE OF ENDOTHELIN-1 INSICKLEACUTE CHEST SYNDROMEU54HL070595 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KALRA, VIJAY K. · 2003 to 2007
$8.3M
Role of Placenta Growth factor in Sickle ACSR01HL079916 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI MALIK, PUNAM · 2005 to 2008
$3.3M
NHLBI NIH HHS HL-070595NHLBI NIH HHS R01 HL079916NHLBI NIH HHS R01-HL-079916NHLBI NIH HHS U54 HL070595NIDDK NIH HHS P30 DK048522NIDDK NIH HHS P30-DK 048522
6 · The paper itself

Abstract

Individuals with sickle cell disease (SCD) have increased inflammation, a high incidence of airway hyperreactivity (AH), and increased circulating leukotrienes (LT). We show that expression of 5-lipoxygenase and 5-lipoxygenase activating protein (FLAP), key catalytic molecules in the LT pathway, were significantly increased in peripheral blood mononuclear cells (MNCs) in patients with SCD, compared with healthy controls. Placenta growth factor (PlGF), elaborated from erythroid cells, activated MNC and THP-1 monocytic cells to induce LT production. PlGF-mediated increased FLAP mRNA expression occurred via activation of phosphoinositide-3 (PI-3) kinase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and hypoxia inducible factor-1alpha (HIF-1alpha). HIF-1alpha small interfering RNA (siRNA) reduced PlGF-induced FLAP expression. FLAP promoter-driven luciferase constructs demonstrated that PlGF-mediated luciferase induction was abrogated upon mutation of HIF-1alpha response element (HRE), but not the nuclear factor-kappaB (NF-kappaB) site in the FLAP promoter; a finding confirmed by chromatin immunoprecipitation (ChIP) analysis. PlGF also increased HIF-1alpha binding to the HRE in the FLAP promoter. Therefore, it is likely that the intrinsically elevated levels of PlGF in SCD subjects contribute to increased LT, which in turn, mediate both inflammation and AH. Herein, we identify a mechanism of increased LT in SCD and show HIF-1alpha as a hypoxia-independent target of PlGF. These studies provide new avenues to ameliorate these complications.

Indexed as

Gene Expression Regulation5-Lipoxygenase-Activating ProteinsAnemia, Sickle CellArachidonate 5-LipoxygenaseCarrier ProteinsCell LineChildChild, PreschoolFemaleHumansHypoxia-Inducible Factor 1, alpha SubunitLeukotrienesMaleMembrane ProteinsNADPH OxidasesNF-kappa B5-Lipoxygenase-Activating ProteinsALOX5AP protein, humanArachidonate 5-LipoxygenaseCarrier ProteinsHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitLeukotrienesMembrane ProteinsNADPH OxidasesNF-kappa BPGF protein, humanPhosphatidylinositol 3-KinasesPlacenta Growth FactorPregnancy Proteins

Identifiers

PMID18945963
PMCPMC2635078
OpenAlexW2051114755

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.