Evidence map›Paper›PMID 22445600›Full record

ArticleCell metabolism2012

Macrophage autophagy plays a protective role in advanced atherosclerosis.

Xianghai Liao, Judith C Sluimer, Ying Wang, Manikandan Subramanian, Kristy Brown, J Scott Pattison, Jeffrey Robbins, Jennifer Martinez, Ira Tabas

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03700424 (The Use of Intravenous Trehalose to Reduce Vascular Inflammation in Acute Coronary Syndrome), which is not on this map. Cited by 354 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
354citing papers in PubMed, 1 pooled it
15.9field-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.

NCT03700424 phase2unknown statusnot on this mapstarted 2020, after this paper: background citation

The Use of Intravenous Trehalose to Reduce Vascular Inflammation in Acute Coronary Syndrome

TypeinterventionalSponsorMashhad University of Medical SciencesRan2020 to 2022Enrolled15ConditionsAcute Coronary SyndromeArmsTrehalose, Normal saline
3 · Its place in the literature

Who cites it

354 citing papers in PubMed, 1 synthesis or guideline pooled it, 615 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. From lipid overload to autophagy collapse: how lipid dysregulation drives chronic inflammation and metabolic disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Anti-Atherogenic Mechanisms and Therapies.Current atherosclerosis reports · 2025
    Review
  19. Biological Modulation of Autophagy by Nanoplastics: A Current Overview.International journal of molecular sciences · 2025
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Xianghai LiaoDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Judith C Sluimer
Ying Wang
Manikandan Subramanian
Kristy Brown
J Scott Pattison
Jeffrey Robbins
Jennifer Martinez
Ira Tabas
Columbia University · USCincinnati Children's Hospital Medical Center · USSt. Jude Children's Research Hospital · US

Funding

TTC39B in obesity and atherosclerosisP01HL087123 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TALL, ALAN RICHARD · 2007 to 2022
$31.2M
Regulation and function of plasma lipid transfer proteinsP01HL054591 · NHLBI · ROCKEFELLER UNIVERSITY · PI TALL, ALAN RICHARD · 1995 to 2010
$19.9M
The Unfolded Protein Response in Sterol CytoxicityR01HL075662 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TABAS, IRA A · 2004 to 2017
$5.6M
Autophagy in Advanced AtherosclerosisR01HL106019 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TABAS, IRA A · 2011 to 2014
$1.8M
Mechanisms of Defective Efferocytosis in AtherosclerosisR01HL107497 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TABAS, IRA A · 2012 to 2015
$1.6M
Characterization of LC3-Associated PhagocytosisF32AI091306 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI MARTINEZ, JENNIFER · 2011 to 2013
$155k
NHLBI NIH HHS HL054591NHLBI NIH HHS HL075662NHLBI NIH HHS HL106019NHLBI NIH HHS P01 HL054591NHLBI NIH HHS P01 HL087123NHLBI NIH HHS R01 HL075662NHLBI NIH HHS R01 HL106019NHLBI NIH HHS R01 HL107497NIAID NIH HHS F32 AI091306
6 · The paper itself

Abstract

In advanced atherosclerosis, macrophage apoptosis coupled with defective phagocytic clearance of the apoptotic cells (efferocytosis) promotes plaque necrosis, which precipitates acute atherothrombotic cardiovascular events. Oxidative and endoplasmic reticulum (ER) stress in macrophages are important causes of advanced lesional macrophage apoptosis. We now show that proapoptotic oxidative/ER stress inducers trigger another stress reaction in macrophages, autophagy. Inhibition of autophagy by silencing ATG5 or other autophagy mediators enhances apoptosis and NADPH oxidase-mediated oxidative stress while at the same time rendering the apoptotic cells less well recognized by efferocytes. Most importantly, macrophage ATG5 deficiency in fat-fed Ldlr(-/-) mice increases apoptosis and oxidative stress in advanced lesional macrophages, promotes plaque necrosis, and worsens lesional efferocytosis. These findings reveal a protective process in oxidatively stressed macrophages relevant to plaque necrosis, suggesting a mechanism-based strategy to therapeutically suppress atherosclerosis progression and its clinical sequelae.

Indexed as

AutophagyCytoprotectionAnimalsApoptosisAtherosclerosisMacrophagesMiceMice, Inbred C57BLMice, TransgenicNADPH OxidasesNecrosisOxidative StressPhagocytosisPlaque, AtheroscleroticNADPH Oxidases

Identifiers

PMID22445600
PMCPMC3322248
OpenAlexW1989605865

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

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.