Evidence mapPaperPMID 41402252Full record

ArticleNature communications2025

MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages.

Zhuo Du, Pingping Wan, Manyu Du, Song Li, Qiuying Yan, Sibo Sun, Caiying Tang, Ziquan Jiang, Shuang Li, Guoxia Shi and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

19 authors.

Zhuo Du *Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Pingping Wan *Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Manyu DuDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Song LiDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Qiuying YanDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Sibo SunDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Caiying TangDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Ziquan JiangDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Shuang LiDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Guoxia ShiDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Baixue MiaoDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Xiaoyu DuDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Shilong LiDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Shaohong FangDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Chao WangThe Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.
Chao FangDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.ORCID http://orcid.org/0009-0001-2340-9373
Bo YuDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China. yubodr@163.com.ORCID http://orcid.org/0000-0002-5955-6332
Jiannan DaiDepartment of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China. daijiannandr@163.com.ORCID http://orcid.org/0009-0005-4949-4413
Ping SunThe Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. sunpinghmu@163.com.ORCID http://orcid.org/0000-0002-5487-9503

Funding

National Natural Science Foundation of China (National Science Foundation of China) 62135002National Natural Science Foundation of China (National Science Foundation of China) 82072091National Natural Science Foundation of China (National Science Foundation of China) 82202286National Natural Science Foundation of China (National Science Foundation of China) 82322036National Natural Science Foundation of China (National Science Foundation of China) 82471998
6 · The paper itself

Abstract

Atherosclerosis is mediated by circulating monocytes and lesional macrophages through chronic inflammation accompanied by metabolic reprogramming. Although methionine metabolism enhances the proinflammatory capacity of monocytes/macrophages, its role in atherosclerosis remains unclear. Here, we use untargeted metabolomics and mass spectrometry to demonstrate that monocyte methionine metabolism is associated with vulnerable plaque (thin-cap fibroatheroma [TCFA]) identified by pancoronary optical coherence tomography. Methionine adenosyltransferase Ⅱ alpha (MAT2A), the key enzyme of methionine metabolism, is highly expressed in atherosclerosis. Further epigenetic profiling of inflammatory and migratory gene promoters reveals MAT2A-mediated enrichment of the transcriptional permissive chromatin mark H3K4me3. Myeloid-specific MAT2A ablation and pharmacological inhibition, or a low-methionine diet, reduce monocyte/macrophage inflammation and migration, thereby attenuating plaque vulnerability. Mechanistically, norepinephrine activates the mTOR-c-MYC axis to upregulate MAT2A expression. The combination of norepinephrine and methionine metabolism is associated with TCFA presence and 5-year clinical prognosis. Consequently, MAT2A-mediated methionine metabolism represents a potential therapeutic target for atherosclerosis.

Indexed as

AtherosclerosisEpigenesis, GeneticMacrophagesMethionine AdenosyltransferasePlaque, AtheroscleroticAnimalsCellular ReprogrammingFemaleHistonesHumansMaleMethionineMiceMice, Inbred C57BLMice, KnockoutMonocyteshistone H3 trimethyl Lys4HistonesMAT2A protein, humanMethionineMethionine AdenosyltransferaseProto-Oncogene Proteins c-mycTOR Serine-Threonine Kinases

Identifiers

PMID41402252
PMCPMC12708628

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.