Evidence map›Paper›PMID 27384322›Full record

ArticleCirculation research2016

Ogg1-Dependent DNA Repair Regulates NLRP3 Inflammasome and Prevents Atherosclerosis.

Gantsetseg Tumurkhuu, Kenichi Shimada, Jargalsaikhan Dagvadorj, Timothy R Crother, Wenxuan Zhang, Daniel Luthringer, Roberta A Gottlieb, Shuang Chen, Moshe Arditi

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed
7.8field-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

102 citing papers in PubMed, 179 citations in OpenAlex.

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  7. 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025
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42 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 2 institutions in 1 country.

Gantsetseg TumurkhuuFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).
Kenichi ShimadaFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).
Jargalsaikhan DagvadorjFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).
Timothy R CrotherFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).
Wenxuan ZhangFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).
Daniel LuthringerFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).
Roberta A GottliebFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).
Shuang ChenFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.).
Moshe ArditiFrom the Departments of Pediatrics, Biomedical Sciences, and Infectious and Immunologic Diseases Research Center (IIDRC) (G.T., K.S., J.D., T.R.C., W.Z., S.C.), Department of Pathology (D.L.), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Medicine, Barbra Streisand Women's Heart Center, Heart Institute of Cedars-Sinai (R.A.G.), Cedars-Sinai Medical Center, Los Angeles, CA; and David Geffen School of Medicine, University of California, Los Angeles (M.A.). moshe.arditi@cshs.org.
Cedars-Sinai Medical Center · USCedars-Sinai Smidt Heart Institute · US

Funding

Protein Chemistry and ProteomicsP01HL112730 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI VAN EYK, JENNIFER E · 2013 to 2017
$12.0M
MOLECULAR PATHOGENESIS OF CHLAMYDIA-INDUCED ATHEROGENESIR01HL066436 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI ARDITI, MOSHE · 2001 to 2013
$3.6M
Sequential release of IL-1alpha and IL-1beta leads to a two-hit model of acute lung injuryR01HL130353 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI SHIMADA, KENICHI · 2016 to 2020
$2.2M
Mitochondrial Turnover in the Human HeartR01HL132075 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI GOTTLIEB, ROBERTA A., VAN EYK, JENNIFER E · 2017 to 2020
$2.1M
Innate Immunity and Pathogen mediated Acceleration in Vascular InflammationR01HL111483 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI CHEN, SHUANG · 2012 to 2016
$2.0M
Mitochondrial DNA Damage and Inflammasome Activation in Vascular InflammationR21AI105845 · NIAID · CEDARS-SINAI MEDICAL CENTER · PI ARDITI, MOSHE · 2014 to 2015
$459k
NHLBI NIH HHS P01 HL112730NHLBI NIH HHS R01 HL066436NHLBI NIH HHS R01 HL111483NHLBI NIH HHS R01 HL130353NHLBI NIH HHS R01 HL132075NIAID NIH HHS R21 AI105845
6 · The paper itself

Abstract

rationaleActivation of NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome-mediating interleukin (IL)-1β secretion has emerged as an important component of inflammatory processes in atherosclerosis. Mitochondrial DNA (mtDNA) damage is detrimental in atherosclerosis, and mitochondria are central regulators of the nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 inflammasome. Human atherosclerotic plaques express increased mtDNA damage. The major DNA glycosylase, 8-oxoguanine glycosylase (OGG1), is responsible for removing the most abundant form of oxidative DNA damage.

objectiveTo test the role of OGG1 in the development of atherosclerosis in mouse. METHODS AND

resultsWe observed that Ogg1 expression decreases over time in atherosclerotic lesion macrophages of low-density lipoprotein receptor (Ldlr) knockout mice fed a Western diet. Ogg1(-/-)Ldlr(-/-) mice fed a Western diet resulted in an increase in plaque size and lipid content. We found increased oxidized mtDNA, inflammasome activation, and apoptosis in atherosclerotic lesions and also higher serum IL-1β and IL-18 in Ogg1(-/-)Ldlr(-/-) mice than in Ldlr(-/-). Transplantation with Ogg1(-/-) bone marrow into Ldlr(-/-) mice led to larger atherosclerotic lesions and increased IL-1β production. However, transplantation of Ogg1(-/-)Nlrp3(-/-) bone marrow reversed the Ogg1(-/-) phenotype of increased plaque size. Ogg1(-/-) macrophages showed increased oxidized mtDNA and had greater amounts of cytosolic mtDNA and cytochrome c, increased apoptosis, and more IL-1β secretion. Finally, we found that proatherogenic miR-33 can directly inhibit human OGG1 expression and indirectly suppress both mouse and human OGG1 via AMP-activated protein kinase.

conclusionsOGG1 plays a protective role in atherogenesis by preventing excessive inflammasome activation. Our study provides insight into a new target for therapeutic intervention based on a link between oxidative mtDNA damage, OGG1, and atherosclerosis via NLRP3 inflammasome.

Indexed as

AnimalsAtherosclerosisDiet, WesternDNA GlycosylasesDNA, MitochondrialDNA RepairHumansInflammasomesMiceMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinDNA GlycosylasesDNA, MitochondrialInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseOgg1 protein, mouseatherosclerosisDNA repairinflammasomesmacrophagesmitochondria

Identifiers

PMID27384322
PMCPMC5010464
OpenAlexW2461916920

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Registered trials

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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.