Evidence map›Paper›PMID 39411860›Full record

ArticleCirculation2024

Extracellular RIPK3 Acts as a Damage-Associated Molecular Pattern to Exaggerate Cardiac Ischemia/Reperfusion Injury.

Wenjia Zhang, Junxia Zhang, Zeyuan Wang, Ting Li, Changyun Liu, Xuya Kang, Xiaomeng Cui, Jingli Yang, Huilin Qu, Jiaxin Duanmu and 23 more

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Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

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0cells of the map it votes in
26citing 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

26 citing papers in PubMed.

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  16. The impact of lipid metabolism on ferroptosis in myocardial ischemia-reperfusion injury.Apoptosis : an international journal on programmed cell death · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Wenjia Zhang *Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).ORCID 0000-0002-9299-6137
Junxia Zhang *Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).ORCID 0000-0001-7841-8675
Zeyuan Wang *Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing (Z.W., Z.T., Z.L., Y.J., Y.S., X.H., S.Z.).ORCID 0000-0002-8384-2574
Ting Li *Department of Cardiology, First Affiliated Hospital, Xi'an Jiaotong University, China (T.L., X.Z., Y.W.).ORCID 0000-0003-1377-8076
Changyun LiuInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).ORCID 0000-0002-1393-7578
Xuya KangInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).ORCID 0000-0002-6593-5347
Xiaomeng CuiInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).
Jingli YangInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).ORCID 0009-0007-1250-8345
Huilin QuInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).
Jiaxin DuanmuInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).
Ying PengDepartment of General Surgery (Y.P), Peking University Third Hospital, Beijing, China.
Kai WangDepartment of Hysiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Female Fertility Promotion, Center for Reproductive III Medicine (K.W.), Peking University, Beijing, China.ORCID 0000-0001-9705-6366
Li JinState Key Laboratory of Membrane Biology Institute of Molecular Medicine, College of Future Technology (L.J., P.X., W. Zheng, H.S., X.H.), Peking University, Beijing, China.
Peng XieState Key Laboratory of Membrane Biology Institute of Molecular Medicine, College of Future Technology (L.J., P.X., W. Zheng, H.S., X.H.), Peking University, Beijing, China.
Wen ZhengState Key Laboratory of Membrane Biology Institute of Molecular Medicine, College of Future Technology (L.J., P.X., W. Zheng, H.S., X.H.), Peking University, Beijing, China.
Haibao ShangState Key Laboratory of Membrane Biology Institute of Molecular Medicine, College of Future Technology (L.J., P.X., W. Zheng, H.S., X.H.), Peking University, Beijing, China.
Yahan LiuInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).
Zhuang TianDepartment of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing (Z.W., Z.T., Z.L., Y.J., Y.S., X.H., S.Z.).ORCID 0000-0003-1140-4062
Zhenyu LiuDepartment of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing (Z.W., Z.T., Z.L., Y.J., Y.S., X.H., S.Z.).ORCID 0000-0001-5077-5777
Ye JinDepartment of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing (Z.W., Z.T., Z.L., Y.J., Y.S., X.H., S.Z.).
Yingjia LiInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).
Nan LiResearch Center of Clinical Epidemiology (N.L.), Peking University Third Hospital, Beijing, China.ORCID 0000-0003-4231-8853
Xiaozhen ZhuoDepartment of Cardiology, First Affiliated Hospital, Xi'an Jiaotong University, China (T.L., X.Z., Y.W.).ORCID 0000-0002-9858-8409
Yue WuDepartment of Cardiology, First Affiliated Hospital, Xi'an Jiaotong University, China (T.L., X.Z., Y.W.).ORCID 0000-0002-0084-2510
Xiaolu ShiState Key Laboratory of Membrane Biology Institute of Molecular Medicine, College of Future Technology (L.J., P.X., W. Zheng, H.S., X.H.), Peking University, Beijing, China.ORCID 0000-0002-5351-0894
Runhao MaBeijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Disease, Experimental Research Center, China Academy of Chinese Medical Sciences (X.S., R.M.).
Yueshen SunDepartment of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing (Z.W., Z.T., Z.L., Y.J., Y.S., X.H., S.Z.).ORCID 0000-0002-8757-1417
Kai ZhangDepartment of Anesthesiology and Intensive Care, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China (K.Z., X.F.).ORCID 0000-0002-2558-0676
Xiangming FangDepartment of Anesthesiology and Intensive Care, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China (K.Z., X.F.).
Xiaomin HuDepartment of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing (Z.W., Z.T., Z.L., Y.J., Y.S., X.H., S.Z.).
Erdan DongInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).ORCID 0009-0006-8737-5308
Shuyang ZhangDepartment of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing (Z.W., Z.T., Z.L., Y.J., Y.S., X.H., S.Z.).
Yan ZhangInstitute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center (W. Zhang, J.Z., C.L., X.K., X.C., J.Y, H.Q., J.D., Y. Liu, Y. Li, E.D., Y.Z).ORCID 0000-0002-8322-467X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease. Currently, there is no effective therapy for reducing cardiac I/R injury. Damage-associated molecular patterns are endogenous molecules released after cellular damage to exaggerate tissue inflammation and injury. RIPK3 (receptor-interacting protein kinase 3), a well-established intracellular mediator of cell necroptosis and inflammation, serves as a circulating biomarker of multiple diseases. However, whether extracellular RIPK3 also exerts biological functions in cardiac I/R injury remains totally unknown.

methodsPatients with acute myocardial infarction receiving percutaneous coronary intervention (PCI) were recruited independently in the discovery cohort (103 patients) and validation cohort (334 patients), and major adverse cardiovascular events were recorded. Plasma samples were collected before and after PCI (6 and 24 h) for RIPK3 concentration measurement. Cultured neonatal rat ventricular myocytes, macrophages and endothelial cells, and in vivo mouse models with myocardial injury induced by I/R (or hypoxia/reoxygenation) were used to investigate the role and mechanisms of extracellular RIPK3. Another cohort including patients with acute myocardial infarction receiving PCI and healthy volunteers was recruited to further explore the mechanisms of extracellular RIPK3.

resultsIn the discovery cohort, elevated plasma RIPK3 levels after PCI are associated with poorer short- and long-term outcomes in patients with acute myocardial infarction, as confirmed in the validation cohort. In both cultured cells and in vivo mouse models, recombinant RIPK3 protein exaggerated myocardial I/R (or hypoxia/reoxygenation) injury, which was alleviated by the RIPK3 antibody. Mechanistically, RIPK3 acted as a damage-associated molecular pattern and bound with RAGE (receptor of advanced glycation end-products), subsequently activating CaMKII (Ca

conclusionsWe identified the positive relationship between plasma RIPK3 concentrations and the risk of major adverse cardiovascular events in patients with acute myocardial infarction receiving PCI. As a damage-associated molecular pattern, extracellular RIPK3 plays a causal role in multiple pathological conditions during cardiac I/R injury through RAGE/CaMKII signaling. These findings expand our understanding of the physiological and pathological roles of RIPK3, and also provide a promising therapeutic target for myocardial I/R injury and the associated complications.

Indexed as

Myocardial Reperfusion InjuryReceptor-Interacting Protein Serine-Threonine KinasesAgedAnimalsBiomarkersDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMiddle AgedMyocardial InfarctionMyocytes, CardiacPercutaneous Coronary InterventionRatsBiomarkersReceptor-Interacting Protein Serine-Threonine KinasesRIPK3 protein, humanRipk3 protein, mouseCaMKIIdamage-associated molecular patternheartischemia/reperfusion injuryreceptor-interacting protein kinase 3

Identifiers

PMID39411860

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