Evidence mapPaperPMID 41736666Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

PAF Triggered Pyroptotic NETosis Aggravates Myocardial Ischemia/Reperfusion Injury.

Jiawei Wu, Shule Zhang, Ruofan Du, Lina Kang, Guodong Zhao, Xue Bao, Haochi Yang, Ziqing Xie, Tianyu He, Huiyong Sun and 2 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Jiawei WuState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
Shule ZhangState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
Ruofan DuState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
Lina KangDepartment of Cardiology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.
Guodong ZhaoState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
Xue BaoDepartment of Cardiology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.
Haochi YangState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
Ziqing XieState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
Tianyu HeState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
Huiyong SunJiangsu Provincial Key Laboratory of Targetome and Innovative Drugs, Institute of Innovative Drug, China Pharmaceutical University, Nanjing, P. R. China.
Haiping HaoState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
Lijuan CaoState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.ORCID https://orcid.org/0000-0002-3834-5018

Funding

CAMS Innovation Fund for Medical Sciences SZSM202301035Foundation Research Project of Jiangsu Province BK20253058National Key Research and Development Programme of China 2021YFA1301300National Key Research and Development Programme of China 2022YFF1100601National Natural Science Foundation of China 82321005National Natural Science Foundation of China 82373886Outstanding Youth Foundation of Jiangsu Province BK20250097Overseas Expertise Introduction Project for Discipline Innovation G20582017001
6 · The paper itself

Abstract

Myocardial ischemia-reperfusion (MI/R) injury remains a critical challenge in cardiovascular therapeutics, with metabolic-inflammatory signaling axis emerging as a critical mediator of pathological outcomes. Yet, the specific metabolic pathways interplay with inflammation to exacerbate MI/R injury remain poorly defined. Here we verify that NETosis of neutrophils is an initiative and causal factor in driving MI/R injury, specifically, platelet activating factor (PAF) secreted by cardiomyocytes during MI/R, drives neutrophil extracellular traps (NETs) formation and subsequent NETosis. Increased expression of PAF synthesis enzyme PLA2G6 explains excessive production of PAF. PAF-induced NETosis requires gasdermin D (GSDMD) mediated pore-forming to facilitate NETs extrusion. Both inhibiting NETs and PAF synthesis significantly alleviate MI/R injury. We further identify dapagliflozin as a potent NETosis inhibitor that protects mice from MI/R injury in a sodium-glucose co-transporter 2 (SGLT2)-independent manner, which targets neutrophil gelatinase-associated lipocalin-2 (LCN2). Notably, increased serum PAF concentration in acute myocardial infarction patients with percutaneous coronary intervention was positively correlated with NETosis and myocardial injury indexes. Of interest, patients receiving dapagliflozin exhibited attenuated myocardial injury in comparison to those without dapagliflozin. Collectively, our study demonstrates PAF serves as a danger signal in triggering NETosis in early MI/R injury, and manipulating PAF-NETosis signal by dapagliflozin or LCN2 inhibitor might be effective in combating MI/R injury.

Indexed as

Extracellular TrapsMyocardial Reperfusion InjuryPlatelet Activating FactorAnimalsBenzhydryl CompoundsDisease Models, AnimalGlucosidesHumansMaleMiceMice, Inbred C57BLMyocytes, CardiacNeutrophilsBenzhydryl CompoundsdapagliflozinGlucosidesPlatelet Activating Factordapagliflozinmyocardial ischemia‐reperfusion injuryNETosisplatelet activating factor

Identifiers

PMID41736666
PMCPMC13137845

What Socratic holds

Textmetadata
LicenceCC BY
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.