Evidence map›Paper›PMID 33232283›Full record

ArticleAging2020

Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway.

Jing Zhang, Lelin Huang, Xing Shi, Liu Yang, Fuzhou Hua, Jianyong Ma, Wengen Zhu, Xiao Liu, Rui Xuan, Yunfeng Shen and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.

0numbers the graph read from it
0cells of the map it votes in
143citing papers in PubMed
20.9field-weighted citation impact, top 1% 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

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

143 citing papers in PubMed, 255 citations in OpenAlex.

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83 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 2 countries.

Jing ZhangDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Jiangxi 3300063, Nanchang, China.
Lelin HuangDepartment of Anesthesiology, Lushan Rehabilitation and Recuperation Center, PLA Joint Service Forces, Jiujiang 3320000, China.
Xing ShiDepartment of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Jiangxi 330006, Nanchang, China.
Liu YangDepartment of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Jiangxi 330006, Nanchang, China.
Fuzhou HuaDepartment of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Jiangxi 3300063, Nanchang, China.
Jianyong MaDepartment of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Wengen ZhuDepartment of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China.
Xiao LiuDepartment of Cardiology, The Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China.
Rui XuanDepartment of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Jiangxi 330006, Nanchang, China.
Yunfeng ShenDepartment of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Jiangxi 330006, Nanchang, China.
Jianping LiuDepartment of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Jiangxi 330006, Nanchang, China.
Xiaoyang LaiDepartment of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Jiangxi 330006, Nanchang, China.
Peng YuDepartment of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Jiangxi 330006, Nanchang, China.
Second Affiliated Hospital of Nanchang University · CNNanchang University · CNSun Yat-sen University · CNUniversity of Cincinnati Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ischemia/reperfusion (I/R) injury is a life-threatening vascular emergency following myocardial infarction. Our previous study showed cardioprotective effects of metformin against myocardial I/R injury. In this study, we further examined the involvement of AMPK mediated activation of NLRP3 inflammasome in this cardioprotective effect of metformin. Myocardial I/R injury was simulated in a rat heart Langendorff model and neonatal rat ventricle myocytes (NRVMs) were subjected to hypoxi/reoxygenation (H/R) to establish an in vitro model. Outcome measures included myocardial infarct size, hemodynamic monitoring, myocardial tissue injury, myocardial apoptotic index and the inflammatory response. myocardial infarct size and cardiac enzyme activities. First, we found that metformin postconditioning can not only significantly alleviated myocardial infarct size, attenuated cell apoptosis, and inhibited myocardial fibrosis. Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and decreased NLRP3 inflammasome activation. In isolated NRVMs metformin increased cellular viability, decreased LDH activity and inhibited cellular apoptosis and inflammation. Importantly, inhibition of AMPK phosphorylation by Compound C (CC) resulted in decreased survival of cardiomyocytes mainly by inducing the release of inflammatory cytokines and increasing NLRP3 inflammasome activation. Finally, in vitro studies revealed that the NLRP3 activator nigericin abolished the anti-inflammatory effects of metformin in NRVMs, but it had little effect on AMPK phosphorylation. Collectively, our study confirmed that metformin exerts cardioprotective effects by regulating myocardial I/R injury-induced inflammatory response, which was largely dependent on the enhancement of the AMPK pathway, thereby suppressing NLRP3 inflammasome activation.

Indexed as

AMP-Activated Protein KinasesAnimalsAnti-Inflammatory AgentsCells, CulturedCytokinesDisease Models, AnimalEnzyme ActivationHemodynamicsInflammasomesInflammation MediatorsIsolated Heart PreparationMaleMetforminMyocardial InfarctionMyocardial Reperfusion InjuryMyocytes, CardiacAMP-Activated Protein KinasesAnti-Inflammatory AgentsCytokinesInflammasomesInflammation MediatorsMetforminNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratAPMKmetforminmyocardial ischemia reperfusion injuryNLRP3pyroptosis

Identifiers

PMID33232283
PMCPMC7762510
OpenAlexW3110200930

What OpenQuestion holds

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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 OpenQuestion graph.