Evidence mapPaperPMID 39674499Full record

ArticleJournal of advanced research2025

Macrophage P2Y12 regulates iron transport and its inhibition protects against atherosclerosis.

Yang-Xi Hu, Hong-Min You, Mei-Rong Bai, Wen-Heng Yue, Fang-Fang Li, Bo-Wen Hu, Ya-Sha Chen, Xiang-Yu Shen, Yue Wu, Jia-Mei Wang and 4 more

Abstract read
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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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

14 authors.

Yang-Xi HuDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Hong-Min YouDepartment of Cardiology, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China.
Mei-Rong BaiDepartment of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
Wen-Heng YueDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Fang-Fang LiCAS Key Laboratory of Tissue Microenvironment and Tumor, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Department of Cardiology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.
Bo-Wen HuDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Ya-Sha ChenDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Xiang-Yu ShenDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Yue WuDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Jia-Mei WangDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Zhi-Qing HeDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Xia TaoDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China. Electronic address: taoxia@smmu.edu.cn.
Qing JingCAS Key Laboratory of Tissue Microenvironment and Tumor, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: qjing@sibs.ac.cn.
Chun LiangDepartment of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China. Electronic address: chunliangliang1985@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionIron retention is commonly observed in atherosclerotic plaques and is believed to be detrimental to atherosclerosis. Platelet P2Y12 is a target of antiplatelet therapy in preventing thrombotic complications of atherosclerosis. The protective effect of P2Y12 on hematopoiesis reported by our previous work implies the involvement of P2Y12 in iron metabolism.

objectivesThis study further investigated the role of P2Y12 in the iron metabolism of macrophages, the key player in systemic iron homeostasis and atherosclerosis.

methodsThe association between serum iron and the use of P2Y12 inhibitors was evaluated by a case-control study in human. Secondary iron overload and atherosclerosis animal models were established in P2Y12-deficient zebrafish to explore the role of P2Y12 in macrophage iron metabolism in vivo. Both iron-overloaded murine primary peritoneal macrophages (PMs) and ox-LDL-treated PMs with P2Y12 knockdown were used for in vitro studies. RNA sequencing and pharmacological approaches were performed to investigate the downstream mechanisms.

resultsIncreased serum iron level was positively associated with P2Y12 inhibitor usage [odds ratio (OR) = 10.333 (1.281-83.370)]. Elevated serum iron level and transferrin saturation, reduced hepatic and splenic iron content, and decreased iron staining in macrophages were observed in secondary iron overload P2Y12-deficient zebrafish. Deficiency of P2Y12 in ApoEb

conclusionP2Y12 inhibition decreased hepcidin autocrine through repressing NF-κB p65 phosphorylation in macrophages, preventing intracellular iron retention and atherosclerosis.

Indexed as

AtherosclerosisIronMacrophagesMacrophages, PeritonealReceptors, Purinergic P2Y12AnimalsBiological TransportCase-Control StudiesDisease Models, AnimalFemaleHumansIron OverloadMaleMicePurinergic P2Y Receptor AntagonistsZebrafishIronPurinergic P2Y Receptor AntagonistsReceptors, Purinergic P2Y12Antiplatelet therapyAtherosclerosisFerroptosisIron overloadMacrophageP2Y12

Identifiers

PMID39674499
PMCPMC12793768

What Socratic holds

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LicenceCC BY-NC-ND
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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.