Evidence map›Paper›PMID 35861735›Full record

ArticleCirculation research2022

Flavin Containing Monooxygenase 2 Prevents Cardiac Fibrosis via CYP2J3-SMURF2 Axis.

Cheng Ni, Yongjian Chen, Yinchuan Xu, Jing Zhao, Qingju Li, Changchen Xiao, Yan Wu, Jingyi Wang, Yingchao Wang, Zhiwei Zhong and 11 more

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

Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

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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

23 citing papers in PubMed, 30 citations in OpenAlex.

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  9. FMO2 Promotes Angiogenesis via Regulation of N-Acetylornithine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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  10. Acyl-CoA-binding protein as a driver of pathological aging.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  16. Crosstalk of ubiquitin system and non-coding RNA in fibrosis.International journal of biological sciences · 2024
    Review
  17. Effect of three oral pathogens on the TMA-TMAO metabolic pathway.Frontiers in cellular and infection microbiology · 2024
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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

21 authors at 2 institutions in 3 countries.

Cheng Ni *Department of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Yongjian Chen *Department of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Yinchuan XuDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).ORCID 0000-0001-9472-7507
Jing ZhaoDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).ORCID 0000-0001-8681-3296
Qingju LiDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).ORCID 0000-0002-1128-2459
Changchen XiaoDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Yan WuDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Jingyi WangDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Yingchao WangDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Zhiwei ZhongDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Ling ZhangDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Rongrong WuDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Qingnian LiuDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Xianpeng WuDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Changle KeDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Wei ZhuDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).
Jinghai ChenDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).ORCID 0000-0002-5401-047X
Jijun HuangDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine, University of California at Los Angeles (J.H.).
Yibin WangProgramme in Cardiovascular and Metabolic Diseases, Duke-NUS Medical School, Singapore (Yibin Wang).ORCID 0000-0003-0852-0767
Jian'an WangDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).ORCID 0000-0002-4583-3204
Xinyang HuDepartment of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China (C.N., Y.C., Y.X., J.Z., Q. Li, C.X., Y. Wu, Jingyi Wang, Yingchao Wang, Z.Z., L.Z., R.W., Q. Liu, X.W., C.K., W.Z., J.C., Jian'an Wang, X.H.).ORCID 0000-0002-6699-8470
World Wide Web Consortium · USUniversity of California, Los Angeles · US

Funding

STRESS ACTIVATED MAP KINASES IN HEART FAILURER01HL062311 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI WANG, YIBIN · 2000 to 2008
$1.9M
NHLBI NIH HHS R01 HL062311
6 · The paper itself

Abstract

backgroundCardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) as a top-ranked gene dynamically expressed following myocardial infarction (MI) in hearts across different species including rodents, nonhuman primates, and human. However, the functional role of FMO2 in cardiac remodeling is largely unknown.

methodsSingle-nuclei transcriptome analysis was performed to identify FMO2 after MI; FMO2 ablation rats were generated both in genetic level using the CRISPR-cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) technology and lentivirus-mediated manner. Gain-of-function experiments were conducted using

resultsA significant downregulation of FMO2 was consistently observed in hearts after MI in rodents, nonhuman primates, and patients. Single-nuclei transcriptome analysis showed cardiac expression of FMO2 was enriched in fibroblasts rather than myocytes. Elevated spontaneous tissue fibrosis was observed in the FMO2-null animals without external stress. In contrast, fibroblast-specific expression of FMO2 markedly reduced cardiac fibrosis following MI in rodents and nonhuman primates associated with diminished SMAD2/3 phosphorylation. Unexpectedly, the FMO2-mediated regulation in fibrosis and SMAD2/3 signaling was independent of its enzymatic activity. Rather, FMO2 was detected to interact with CYP2J3 (cytochrome p450 superfamily 2J3). Binding of FMO2 to CYP2J3 disrupted CYP2J3 interaction with SMURF2 (SMAD-specific E3 ubiquitin ligase 2) in cytosol, leading to increased cytoplasm to nuclear translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling.

conclusionsLoss of FMO2 is a conserved molecular signature in postinjury hearts. FMO2 possesses a previously uncharacterized enzyme-independent antifibrosis activity via the CYP2J3-SMURF2 axis. Restoring FMO2 expression exerts potent ameliorative effect against fibrotic remodeling in postinjury hearts from rodents to nonhuman primates. Therefore, FMO2 is a potential therapeutic target for treating cardiac fibrosis following injury.

Indexed as

cytosoldownregulationfibrosishumansmyocardial infarction

Identifiers

PMID35861735
PMCPMC9932658
OpenAlexW4283818354

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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.