Evidence map›Paper›PMID 38724987›Full record

ArticleCardiovascular diabetology2024

MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.

Yuqiong Chen, Su Li, Bo Guan, Xiaopei Yan, Chao Huang, Yingqiang Du, Fan Yang, Nannan Zhang, Yafei Li, Jian Lu and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 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

15 authors.

Yuqiong Chen *Department of Cardiology, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, 215000, Suzhou, Jiangsu Province, China. cosmoscyq@163.com.
Su Li *Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, China.
Bo Guan *Department of Geriatrics, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Xiaopei YanDepartment of Respiratory Medicine, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China.
Chao HuangMinistry of Science and Technology, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, 215002, Suzhou, Jiangsu, China.
Yingqiang DuDepartment of Cardiology, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, 215000, Suzhou, Jiangsu Province, China.
Fan YangDepartment of Endocrinology, Endocrine and Metabolic Disease Medical Center, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, 210008, Nanjing, China.
Nannan ZhangDepartment of Cardiology, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, 215000, Suzhou, Jiangsu Province, China.
Yafei LiDepartment of Cardiology, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, 215000, Suzhou, Jiangsu Province, China.
Jian LuDepartment of Critical Care Medicine, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
Jiankang WangDepartment of Cardiology, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, 215000, Suzhou, Jiangsu Province, China.
Jun ZhangDepartment of Cardiology, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, 215000, Suzhou, Jiangsu Province, China.
Zhangwei ChenDepartment of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, China. chen.zhangwei@zs-hospital.sh.cn.
Chao ChenDepartment of Cardiology, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, 215000, Suzhou, Jiangsu Province, China. chenchao0321@njmu.edu.cn.
Xiangqing KongDepartment of Cardiology, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical University, 215000, Suzhou, Jiangsu Province, China. Kongxq@njmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.

Indexed as

Diabetic CardiomyopathiesDynaminsEndothelial CellsSignal TransductionAnimalsCells, CulturedCoronary CirculationDisease Models, AnimalFerroptosisHumansIntracellular Signaling Peptides and ProteinsMaleMiceMitochondria, HeartProtein Processing, Post-TranslationalProtein Serine-Threonine KinasesDNM1L protein, humanDnm1l protein, mouseDynaminsIntracellular Signaling Peptides and ProteinsMAP4K4 protein, humanProtein Serine-Threonine KinasesCardiac microvascular injuryDiabetic cardiomyopathyDrp1MAP4K4S-nitrosylation

Identifiers

PMID38724987
PMCPMC11084109

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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.