Evidence map›Paper›PMID 25251587›Full record

ArticleEndocrinology2014

Inhibiting DNA Methylation by 5-Aza-2'-deoxycytidine ameliorates atherosclerosis through suppressing macrophage inflammation.

Qiang Cao, Xianfeng Wang, Lin Jia, Ashis K Mondal, Abdoulaye Diallo, Gregory A Hawkins, Swapan K Das, John S Parks, Liqing Yu, Huidong Shi and 2 more

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

Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 2 pooled it
9.1field-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

96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 188 citations in OpenAlex.

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

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

12 authors at 5 institutions in 1 country.

Qiang CaoDepartment of Biology and Center for Obesity Reversal (Q.C., H.S., B.X.), Georgia State University, Atlanta, Georgia; Departments of Internal Medicine (Q.C., X.W., A.K.M., A.D., G.A.H., S.K.D., H.S., B.X.) and Pathology (J.S.P.), Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of Internal Medicine (L.J.), University of Texas, Southwestern Medical Center, Dallas, Texas; Department of Animal and Avian Sciences (L.Y.), University of Maryland, College Park, Maryland; and Department of Biochemistry and Molecular Biology (H.S.), Georgia Regents University, Augusta, Georgia.
Xianfeng Wang
Lin Jia
Ashis K Mondal
Abdoulaye Diallo
Gregory A Hawkins
Swapan K Das
John S Parks
Liqing Yu
Huidong Shi
Hang Shi
Bingzhong Xue
Wake Forest University · USGeorgia Regents Medical Center · USGeorgia State University · USThe University of Texas Southwestern Medical Center · USUniversity of Maryland, College Park · US

Funding

The Role of Hepatocyte ABCA1 in Lipid Mobilization and TransportR01HL119962 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI PARKS, JOHN S · 2013 to 2022
$3.9M
Macrophage AMPK, Inflammation, and AtherosclerosisR01HL107500 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI XUE, BINGZHONG · 2012 to 2016
$1.8M
The AMP-Activated Protein Kinase (AMPK) Antagonizes Inflammation Through SIRT1R01DK084172 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SHI, HANG · 2009 to 2012
$1.2M
NHLBI NIH HHS R01 HL107500NHLBI NIH HHS R01HL107500NHLBI NIH HHS R01 HL119962NIDDK NIH HHS R01 DK084172NIDDK NIH HHS R01DK084172
6 · The paper itself

Abstract

Inflammation marks all stages of atherogenesis. DNA hypermethylation in the whole genome or specific genes is associated with inflammation and cardiovascular diseases. Therefore, we aimed to study whether inhibiting DNA methylation by DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) ameliorates atherosclerosis in low-density lipoprotein receptor knockout (Ldlr(-/-)) mice. Ldlr(-/-) mice were fed an atherogenic diet and adminisered saline or 5-aza-dC (0.25 mg/kg) for up to 30 weeks. 5-aza-dC treatment markedly decreased atherosclerosis development in Ldlr(-/-) mice without changes in body weight, plasma lipid profile, macrophage cholesterol levels and plaque lipid content. Instead, this effect was associated with decreased macrophage inflammation. Macrophages with 5-aza-dC treatment had downregulated expression of genes involved in inflammation (TNF-α, IL-6, IL-1β, and inducible nitric oxidase) and chemotaxis (CD62/L-selectin, chemokine [C-C motif] ligand 2/MCP-1 [CCL2/MCP-1], CCL5, CCL9, and CCL2 receptor CCR2). This resulted in attenuated macrophage migration and adhesion to endothelial cells and reduced macrophage infiltration into atherosclerotic plaques. 5-aza-dC also suppressed macrophage endoplasmic reticulum stress, a key upstream signal that activates macrophage inflammation and apoptotic pathways. Finally, 5-aza-dC demethylated liver X receptor α (LXRα) and peroxisome proliferator-activated receptor γ1 (PPARγ1) promoters, which are both enriched with CpG sites. This led to overexpression of LXRα and PPARγ, which may be responsible for 5-aza-dC's anti-inflammatory and atheroprotective effect. Our findings provide strong evidence that DNA methylation may play a significant role in cardiovascular diseases and serve as a therapeutic target for prevention and treatment of atherosclerosis.

Indexed as

DNA MethylationAnimalsAtherosclerosisAzacitidineCell AdhesionCell MovementCells, CulturedDecitabineEndoplasmic Reticulum StressLipidsLiver X ReceptorsMacrophagesMaleMiceMice, KnockoutOrphan Nuclear ReceptorsAzacitidineDecitabineLipidsLiver X ReceptorsNr1h3 protein, mouseNr1h3 protein, ratOrphan Nuclear ReceptorsPPAR gamma

Identifiers

PMID25251587
PMCPMC4239421
OpenAlexW2004848541

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.