Evidence map›Paper›PMID 23562078›Full record

ArticleCell metabolism2013

Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration.

Abdoulaye Sene, Aslam A Khan, Douglas Cox, Rei E I Nakamura, Andrea Santeford, Bryan M Kim, Rohini Sidhu, Michael D Onken, J William Harbour, Shira Hagbi-Levi and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 2 pooled it
16.9field-weighted citation impact, top 1% 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

174 citing papers in PubMed, 2 syntheses or guidelines pooled it, 269 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. The roles of glycerophospholipids in the aging retina and age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

114 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 2 countries.

Abdoulaye SeneDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Aslam A Khan
Douglas Cox
Rei E I Nakamura
Andrea Santeford
Bryan M Kim
Rohini Sidhu
Michael D Onken
J William Harbour
Shira Hagbi-Levi
Itay Chowers
Peter A Edwards
Angel Baldan
John S Parks
Daniel S Ory
Rajendra S Apte
Washington University in St. Louis · USHadassah Medical Center · ILSaint Louis University · USUniversity of California, Los Angeles · USWake Forest University · US

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 1985 to 2019
$55.2M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Jennifer Lynn Powers Carson · 2013 to 2026
$27.1M
TRANSGENICS COREP60DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI SCHAFFER, JEAN E. · 1986 to 2012
$25.2M
TISSUE CULTURE COREP01HL049373 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SHELNESS, GREGORY S · 1993 to 2012
$23.8M
WASHINGTON UNIVERSITY CENTER VISION RESEARCHP30EY002687 · NEI · WASHINGTON UNIVERSITY · PI Philip Andrew Ruzycki · 1985 to 2026
$18.4M
Post-lysosomal cholesterol trafficking networksR01HL067773 · NHLBI · WASHINGTON UNIVERSITY · PI SCHAFFER, JEAN E. · 2002 to 2021
$6.3M
THE IMPORTANCE OF MACROPHAGE SENESCENCE IN REGULATING ANGIOGENESIS IN THE EYER01EY019287 · NEI · WASHINGTON UNIVERSITY · PI APTE, RAJENDRA S · 2010 to 2021
$3.9M
Control Sterol and Lipoprotein Homeostasis by miRNAR01HL107794 · NHLBI · SAINT LOUIS UNIVERSITY · PI BALDAN, ANGEL · 2011 to 2019
$3.3M
Macrophage, ABCA1, Inflammation, and AtherosclerosisR01HL094525 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI PARKS, JOHN S · 2009 to 2012
$1.5M
Immune Mechanisms in Choroidal NeovascularizationK08EY016139 · NEI · WASHINGTON UNIVERSITY · PI APTE, RAJENDRA S · 2005 to 2009
$1.0M
NEI NIH HHS K08 EY016139NEI NIH HHS K08EY016139NEI NIH HHS P30 EY002687NEI NIH HHS P30EY02687NEI NIH HHS R01 EY019287NEI NIH HHS R01EY019287NHLBI NIH HHS HL-107794NHLBI NIH HHS HL-30568NHLBI NIH HHS P01 HL049373NHLBI NIH HHS P01HL049373NHLBI NIH HHS R01 HL067773NHLBI NIH HHS R01 HL094525NHLBI NIH HHS R01 HL107794NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P60 DK020579
6 · The paper itself

Abstract

Pathologic angiogenesis mediated by abnormally polarized macrophages plays a central role in common age-associated diseases such as atherosclerosis, cancer, and macular degeneration. Here we demonstrate that abnormal polarization in older macrophages is caused by programmatic changes that lead to reduced expression of ATP binding cassette transporter ABCA1. Downregulation of ABCA1 by microRNA-33 impairs the ability of macrophages to effectively efflux intracellular cholesterol, which in turn leads to higher levels of free cholesterol within senescent macrophages. Elevated intracellular lipid polarizes older macrophages to an abnormal, alternatively activated phenotype that promotes pathologic vascular proliferation. Mice deficient for Abca1, but not Abcg1, demonstrate an accelerated aging phenotype, whereas restoration of cholesterol efflux using LXR agonists or miR-33 inhibitors reverses it. Monocytes from older humans with age-related macular degeneration showed similar changes. These findings provide an avenue for therapeutic modulation of macrophage function in common age-related diseases.

Indexed as

AnimalsATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 1Cell ProliferationCells, CulturedCellular SenescenceCholesterolDiet, High-FatEndothelium, VascularHumansLeukocytes, MononuclearLipoproteinsMacrophagesMacular DegenerationMiceABCA1 protein, humanABCG1 protein, mouseATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 1CholesterolLipoproteinsMicroRNAsMirn33 microRNA, mouse

Identifiers

PMID23562078
PMCPMC3640261
OpenAlexW2050546552

What OpenQuestion holds

Textmetadata
LicenceTDM
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.