Evidence map›Paper›PMID 27079462›Full record

ArticleJournal of cellular and molecular medicine2016

Autophagy dysfunction and regulatory cystatin C in macrophage death of atherosclerosis.

Wei Li, Nargis Sultana, Nabeel Siraj, Liam J Ward, Monika Pawlik, Efrat Levy, Stefan Jovinge, Eva Bengtsson, Xi-Ming Yuan

Open access · goldAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

36 citing papers in PubMed, 74 citations in OpenAlex.

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  11. Macrophage Phenotyping in Atherosclerosis by Proteomics.International journal of molecular sciences · 2023
    Review
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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

9 authors at 6 institutions in 3 countries.

Wei LiDivision of Obstetrics and Gynaecology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Nargis SultanaOccupational and Environmental Medicine Center, Heart and Medicine Center, County Council of Östergötland, Linköping, Sweden.
Nabeel SirajOccupational and Environmental Medicine Center, Heart and Medicine Center, County Council of Östergötland, Linköping, Sweden.
Liam J WardDivision of Obstetrics and Gynaecology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Monika PawlikNathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Efrat LevyNathan S. Kline Institute for Psychiatric Research, Departments of Psychiatry and Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY, USA.
Stefan JovingeDepartment of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
Eva BengtssonDepartment of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
Xi-Ming YuanOccupational and Environmental Medicine Center, Heart and Medicine Center, County Council of Östergötland, Linköping, Sweden.
County Administrative Board · SELinköping University · SELund University · SENathan Kline Institute for Psychiatric Research · USNew York University · USSkåne University Hospital · SE

Funding

Uncovering Alzheimer's disease risk mechanisms through neuron-specific analysis of autophagy and endosomal-lysosomal functionP01AG017617 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI NIXON, RALPH A. · 2000 to 2021
$40.0M
NIA NIH HHS P01 AG017617
6 · The paper itself

Abstract

Autophagy dysfunction in mouse atherosclerosis models has been associated with increased lipid accumulation, apoptosis and inflammation. Expression of cystatin C (CysC) is decreased in human atheroma, and CysC deficiency enhances atherosclerosis in mice. Here, we first investigated the association of autophagy and CysC expression levels with atheroma plaque severity in human atherosclerotic lesions. We found that autophagy proteins Atg5 and LC3β in advanced human carotid atherosclerotic lesions are decreased, while markers of dysfunctional autophagy p62/SQSTM1 and ubiquitin are increased together with elevated levels of lipid accumulation and apoptosis. The expressions of LC3β and Atg5 were positively associated with CysC expression. Second, we investigated whether CysC expression is involved in autophagy in atherosclerotic apoE-deficient mice, demonstrating that CysC deficiency (CysC(-/-) ) in these mice results in reduction of Atg5 and LC3β levels and induction of apoptosis. Third, macrophages isolated from CysC(-/-) mice displayed increased levels of p62/SQSTM1 and higher sensitivity to 7-oxysterol-mediated lysosomal membrane destabilization and apoptosis. Finally, CysC treatment minimized oxysterol-mediated cellular lipid accumulation. We conclude that autophagy dysfunction is a characteristic of advanced human atherosclerotic lesions and is associated with reduced levels of CysC. The deficiency of CysC causes autophagy dysfunction and apoptosis in macrophages and apoE-deficient mice. The results indicate that CysC plays an important regulatory role in combating cell death via the autophagic pathway in atherosclerosis.

Indexed as

AutophagyAgedAnimalsApoptosisAtherosclerosisCell LineCystatin CDisease ProgressionHumansIntracellular SpaceLipid PeroxidationLysosomesMacrophagesMicePermeabilityPlaque, AtheroscleroticCystatin CRecombinant Proteinsautophagycystatin Clysosomal membrane permeabilizationmacrophage cell death

Identifiers

PMID27079462
PMCPMC4988293
OpenAlexW2341405266

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.