Evidence map›Paper›PMID 22058424›Full record

ArticleJournal of lipid research2012

Murine bone marrow-derived macrophages differentiated with GM-CSF become foam cells by PI3Kγ-dependent fluid-phase pinocytosis of native LDL.

Joshua J Anzinger, Janet Chang, Qing Xu, Manoj K Barthwal, Thomas Bohnacker, Matthias P Wymann, Howard S Kruth

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

25 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Targeting PI3Kγ in cancer.Trends in cancer · 2025
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. PI3K inhibitors in thrombosis and cardiovascular disease.Clinical and translational medicine · 2020
    Review
  12. Article
  13. Constitutive and stimulated macropinocytosis in macrophages: roles in immunity and in the pathogenesis of atherosclerosis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. 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 3 institutions in 2 countries.

Joshua J AnzingerSection of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Janet Chang
Qing Xu
Manoj K Barthwal
Thomas Bohnacker
Matthias P Wymann
Howard S Kruth
National Institutes of Health · USNational Heart Lung and Blood Institute · USUniversity of Basel · CH

Funding

Light Microscopy CoreZICHL006019 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI COMBS, CHRISTIAN · 2009 to 2025
$29.3M
Electron Microscopy CoreZICHL005906 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI SYED, ZULFEQHAR · 2009 to 2025
$12.9M
Mechanism Of Cholesterol Accumulation In Human AtherosclerosisZIAHL002832 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KRUTH, HOWARD S · 2009 to 2019
$12.3M
Intramural NIH HHS
6 · The paper itself

Abstract

Accumulation of cholesterol by macrophage uptake of LDL is a key event in the formation of atherosclerotic plaques. Previous research has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) is present in atherosclerotic plaques and promotes aortic lipid accumulation. However, it has not been determined whether murine GM-CSF-differentiated macrophages take up LDL to become foam cells. GM-CSF-differentiated macrophages from LDL receptor-null mice were incubated with LDL, resulting in massive macrophage cholesterol accumulation. Incubation of LDL receptor-null or wild-type macrophages with increasing concentrations of ¹²⁵I-LDL showed nonsaturable macrophage LDL uptake that was linearly related to the amount of LDL added, indicating that LDL uptake was mediated by fluid-phase pinocytosis. Previous studies suggest that phosphoinositide 3-kinases (PI3K) mediate macrophage fluid-phase pinocytosis, although the isoform mediating this process has not been determined. Because PI3Kγ is known to promote aortic lipid accumulation, we investigated its role in mediating macrophage fluid-phase pinocytosis of LDL. Wild-type macrophages incubated with LDL and the PI3Kγ inhibitor AS605240 or PI3Kγ-null macrophages incubated with LDL showed an ∼50% reduction in LDL uptake and cholesterol accumulation compared with wild-type macrophages incubated with LDL only. These results show that GM-CSF-differentiated murine macrophages become foam cells by fluid-phase pinocytosis of LDL and identify PI3Kγ as contributing to this process.

Indexed as

AnimalsCell DifferentiationCholesterol, LDLClass Ib Phosphatidylinositol 3-KinaseFoam CellsGranulocyte-Macrophage Colony-Stimulating FactorLipoproteins, LDLMacrophagesMaleMiceMice, Inbred C57BLPinocytosisQuinoxalinesThiazolidinediones5-quinoxalin-6-ylmethylenethiazolidine-2,4-dioneCholesterol, LDLClass Ib Phosphatidylinositol 3-KinaseGranulocyte-Macrophage Colony-Stimulating FactorLipoproteins, LDLPik3cg protein, mouseQuinoxalinesThiazolidinediones

Identifiers

PMID22058424
PMCPMC3244071
OpenAlexW2161711034

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.