Evidence map›Paper›PMID 40425583›Full record

ArticleSignal transduction and targeted therapy2025

Arginase 1 drives mitochondrial cristae remodeling and PANoptosis in ischemia/hypoxia-induced vascular dysfunction.

Han She, Jie Zheng, Guozhi Zhao, Yunxia Du, Lei Tan, Zhe-Sheng Chen, Yinyu Wu, Yong Li, Yiyan Liu, Yue Sun and 5 more

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed.

  1. The oxidative stress paradigm in arbovirus infections: mechanisms and therapeutic insights.Redox report : communications in free radical research · 2026
    Review
  2. Materials today. Bio · 2026
    Article
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  9. Lactylation: a novel post-translational modification for cGAS-STING pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  10. Review
  11. Article
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  14. Article
  15. Review
  16. Article
  17. Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026
    Review
  18. Article
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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

15 authors.

Han She *Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Jie Zheng *Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Guozhi Zhao *Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Yunxia Du *Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Lei TanDepartment of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Zhe-Sheng ChenDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.ORCID 0000-0002-8289-097X
Yinyu WuDepartment of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Yong LiDepartment of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Yiyan LiuShock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Yue SunDepartment of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Yi HuDepartment of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Deyu ZuoDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing University of Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, China. zuodeyu@cqctcm.edu.cn.
Qingxiang MaoDepartment of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, China. qxmao@tmmu.edu.cn.
Liangming LiuShock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, China. lmliu62@tmmu.edu.cn.
Tao LiShock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, China. lt200132@tmmu.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82270523National Natural Science Foundation of China (National Science Foundation of China) 82300561National Natural Science Foundation of China (National Science Foundation of China) 82305006Natural Science Foundation of Chongqing (Natural Science Foundation of Chongqing Municipality) CSTB2023NSCQ-MSX0713
6 · The paper itself

Abstract

Ischemic/hypoxic injury significantly damages vascular function, detrimentally impacting patient outcomes. Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dysfunction. The mechanism of this process remains elusive. Using rat models of ischemia and hypoxic vascular smooth muscle cells (VSMCs), we combined transmission electron microscopy, super-resolution microscopy, and metabolic analysis to analyze the structure and function change of mitochondrial cristae. Multi-omics approaches revealed arginase 1 (Arg1) upregulation in ischemic VSMCs, confirmed by in vivo and in vitro knockout models showing Arg1's protective effects on mitochondrial cristae, mitochondrial and vascular function, and limited the release of mtDNA. Mechanistically, Arg1 interacting with Mic10 led to mitochondrial cristae remodeling, together with hypoxia-induced VDAC1 lactylation resulting in the opening of MPTP and release of mtDNA of VSMCs. The released mtDNA led to PANoptosis of VSMCs via activation of the cGAS-STING pathway. ChIP-qPCR results demonstrated that lactate-mediated Arg1 up-regulation was due to H3K18la upregulation. VSMCs targeted nano-material PLGA-PEI-siRNA@PM-α-SMA (NP-siArg1) significantly improved vascular dysfunction. This study uncovers a new mechanism of vascular dysfunction following ischemic/hypoxic injury: a damaging positive feedback loop mediated by lactate-regulated Arg1 expression between the nucleus and mitochondria, leading to mitochondria cristae disorder and mtDNA release, culminating in VSMCs PANoptosis. Targeting VSMCs Arg1 inhibition offers a potential therapeutic strategy to alleviate ischemia/hypoxia-induced vascular impairments.

Indexed as

ArginaseHypoxiaIschemiaMitochondriaAnimalsDNA, MitochondrialHumansMaleMuscle, Smooth, VascularMyocytes, Smooth MuscleRatsRats, Sprague-DawleyArginaseDNA, Mitochondrial

Identifiers

PMID40425583
PMCPMC12117058

What Socratic holds

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LicenceCC BY
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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 Socratic graph.