Evidence map›Paper›PMID 42176503›Full record

ArticleRedox biology2026

Advanced glycation end-products exacerbate myocardial ischemia/reperfusion injury by promoting mitochondrial oxidative damage and PANoptosis in diabetes mellitus.

Ji'e Yang, Jian Zhang, Rong Huang, Ke Meng, Jiayu Liang, Jingyi Lin, Jingpu Wang, Yiweng Wang, Yang Gao, Yanan Qu and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Ji'e YangDepartment of Cardiology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230000, PR China; Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, 230000, PR China; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Jian ZhangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Rong HuangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Ke MengDepartment of Cardiology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230000, PR China; Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, 230000, PR China.
Jiayu LiangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Jingyi LinDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Jingpu WangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Yiweng WangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Yang GaoDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Yanan QuDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Shiyu HuDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Jiatian CaoDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.
Hao SuDepartment of Cardiology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230000, PR China; Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, 230000, PR China. Electronic address: suhao1081@ustc.edu.cn.
Feng ZhangDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China. Electronic address: zhang.feng@zs-hospital.sh.cn.
Junbo GeDivision of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, 230000, PR China; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai, 200032, PR China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diabetes mellitus exacerbates myocardial ischemia/reperfusion injury (MI/RI), but the underlying mechanisms remain unclear. The present study identifies advanced glycation end-products (AGEs) as a key pathological mediator. Upon hypoxia/reoxygenation (H/R) stimulation, AGEs-primed cardiomyocytes exhibited drastic mitochondrial oxidative damage, characterized by elevated mitochondrial reactive oxygen species (mtROS), loss of mitochondrial membrane potential, depletion of ATP, and increased release of mitochondrial DNA and cytochrome c. Mechanistically, AGEs impaired the mitochondrial antioxidant defense via the RAGE-Nrf2-SOD2 axis. Furthermore, AGEs activated the AIM2-ZBP1 PANoptosome, triggering PANoptosis characterized by concurrent upregulation of cleaved caspase-3, GSDMD, and p-MLKL. Mitochondrial oxidative damage was established as the causal upstream event, as a mitochondria-targeted antioxidant or RAGE silencing attenuated PANoptosis, while mtROS inducer (antimycin A) directly activated PANoptosis. Therapeutically, combination treatment with pyridoxamine (an AGEs inhibitor) and empagliflozin (an SGLT2 inhibitor) in diabetic mice potently suppressed AGEs accumulation, mitigated mitochondrial damage and PANoptosis, and significantly improved cardiac recovery post-MI/R. Thus, targeting the AGEs-mitochondrial damage-PANoptosis axis via combined pyridoxamine and empagliflozin represents a promising strategy to alleviate diabetic MI/RI.

Indexed as

Diabetes Mellitus, ExperimentalGlycation End Products, AdvancedMitochondriaMyocardial Reperfusion InjuryOxidative StressAnimalsGlycated ProteinsHumansMaleMiceMitochondria, HeartMyocytes, CardiacReactive Oxygen SpeciesReceptor for Advanced Glycation End ProductsGlycated ProteinsGlycation End Products, AdvancedReactive Oxygen SpeciesReceptor for Advanced Glycation End ProductsAdvanced glycation end-productsDiabetes mellitusMitochondrial oxidative damageMyocardial ischemia/reperfusion injuryPANoptosis

Identifiers

PMID42176503
PMCPMC13224011

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.