Evidence map›Paper›PMID 39747743›Full record

ArticleCardiovascular drugs and therapy2025

Recombinant dsAAV9-mediated Endogenous Overexpression of Macrophage Migration Inhibitory Factor Alleviates Myocardial Ischemia-Reperfusion Injury via Activating AMPK and ERK1/2 Signaling Pathways.

Xiao-Cui Chen, Min-Tao Gai, Chun-Hui He, Bang-Hao Zhao, Fen Liu, Xiang Ma, Yi-Tong Ma, Xiao-Ming Gao, Bang-Dang Chen

Abstract read
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Article in Cardiovascular drugs and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

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0cells of the map it votes in
5citing 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

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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

5 citing papers in PubMed.

  1. Cardioprotection with Intralipid during CABG.Cardiovascular drugs and therapy · 2026
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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

9 authors.

Xiao-Cui ChenState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China.
Min-Tao GaiState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China.
Chun-Hui HeState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China.
Bang-Hao ZhaoState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China.
Fen LiuState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China.
Xiang MaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China.
Yi-Tong MaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China.
Xiao-Ming GaoState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China. xiaoming.gao@xjmu.edu.cn.
Bang-Dang ChenState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Clinical Medical Research Institute, Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, China. chenbangdang@126.com.ORCID 0000-0002-3473-3718

Funding

Key Program of Natural Science Foundation of Xinjiang Uygur Autonomous Region 2022D01D16National Natural Science Foundation of China 81860072National Natural Science Foundation of China U1903304State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases Fund SKL-HIDCA2021-XXG3State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases Fund SKL-HIDCA-2022-7The Natural Science Foundation of Xinjiang Uygur Autonomous Region 2022D01C768Training Program of National Science Foundation for Distinguished Young Scholar xyd2021J004Xinjiang Uygur Autonomous Region Tianshan Youth Science and Technology Elite Talent Project 2022TSYCCX0031Xinjiang Uygur Autonomous Region Tianshan Youth Science and Technology Elite Talent Project 2023TSYCQNTJ0027
6 · The paper itself

Abstract

purposeTo investigate the protective effect and mechanism of enhanced expression of endogenous macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury.

methodsA recombinant double-stranded adeno-associated virus serotype 9 with MIF or green fluorescent protein (GFP) genes (dsAAV9-MIF/GFP) was transduced into mice and neonatal rat ventricular myocytes (NRVMs). The models of cardiac 60 min ischemia and 24 h reperfusion and 12 h hypoxia/12 h reoxygenation (H/R) were established in mice and NRVMs, respectively. Infarct size, cardiac remodeling, and related signaling pathways were assessed.

resultsThe dsAAV9 vector demonstrated strong transduction efficacy and cardiac affinity. Cardiac overexpression of MIF led to a 35.3% reduction in infarct size and improved cardiac function following I/R injury. In the dsAAV9-MIF group, the AMP-activated protein kinase (AMPK) signaling pathway was activated, and autophagy was enhanced during the ischemic period. During reperfusion, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway was upregulated, leading to reduced cardiac apoptosis. In vitro, transfection with MIF in NRVMs also upregulated AMPK and ERK1/2 signaling during hypoxia and reoxygenation, respectively. Furthermore, MIF overexpression significantly improved autophagy and mitochondrial function, evidenced by an increased LC3-II/I ratio and enhanced mitochondrial membrane potential (ΔΨm), with these effects reversed by the AMPK inhibitor compound C. Additionally, MIF overexpression led to a 60% reduction in the apoptosis rate of cardiomyocytes subjected to H/R and decreased the Bax/Bcl-2 ratio, partially through the ERK1/2 signaling pathway.

conclusionEnhanced endogenous MIF expression via the dsAAV9 vector provides significant cardioprotection against I/R injury by activating the AMPK and ERK1/2 signaling pathways. Our findings suggest that targeting MIF may represent a viable therapeutic strategy for severe and prolonged I/R injury.

Indexed as

AMP-Activated Protein KinasesGenetic TherapyMacrophage Migration-Inhibitory FactorsMyocardial Reperfusion InjurySignal TransductionAnimalsApoptosisAutophagyDependovirusGenetic VectorsMaleMAP Kinase Signaling SystemMembrane Potential, MitochondrialMiceMice, Inbred C57BLMyocytes, CardiacAMP-Activated Protein KinasesMacrophage Migration-Inhibitory FactorsAMP-activated protein kinasesAutophagyExtracellular signal regulated kinaseMacrophage migration-inhibitory factorsMyocardial ischemic reperfusion injury

Identifiers

PMID39747743

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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.