Article in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
0numbers the graph read from it
0cells of the map it votes in
2citing 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.
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
22 authors.
Kun Zhu *Laboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0002-4499-1905
Jing Guo *Laboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.
Yangli LiuLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0002-4081-8291
Jingchen LiLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0003-2371-5095
Xun WangLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0003-4559-5450
Rilei DaiLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0003-1218-2174
Xiang Wei
Dingsheng JiangDivision of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., D.J.).ORCID 0000-0002-0393-3952
Le GaoLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0009-0004-8175-0379
Jiaxing BaiLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0009-0009-5342-3617
Rui CaoLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0009-0006-2269-8122
Zhiheng LinLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0009-0002-6963-0011
Wei ZhouLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0003-1069-1151
Yifan ZhuangLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0009-0008-1612-2287
Yufei WangLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0009-0000-6337-5211
Leilei DuLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0002-2314-5064
Yang LiLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0002-5777-8329
De-Shen LiuLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0003-0661-9886
Weiwei AnLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0009-0006-0788-3629
Qinghua CuiDepartment of Biomedical Informatics, Center for Noncoding RNA Medicine, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, China (Q.C.).ORCID 0000-0003-3018-5221
Weiping LiDepartment of Cardiology (W.L.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0002-5534-5925
Chun-Mei CaoLaboratory of Cardiovascular Science, Beijing Clinical Research Institute (K.Z., J.G., Y. Liu, J.L., X.W., R.D., L.G., J.B., R.C., Z.L., W.Z., Y.Z., Y.W., L.D., Y. Li, D.-S.L., W.A., C.-M.C.), Beijing Friendship Hospital, Capital Medical University, China.ORCID 0000-0002-7162-3104
Funding
No grant is acknowledged in the PubMed record.
6 · The paper itself
Abstract
backgroundMyocardial ischemia/reperfusion (I/R) injury is a common and severe clinical complication in patients with ischemic heart disease after reperfusion therapy. Effective therapeutic strategies for myocardial I/R injury remain limited. Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. However, the mechanisms underlying ferroptosis in myocardial I/R injury are not fully understood.
methodsTranscriptomic data from patients with heart failure and cardiomyocytes undergoing ferroptosis were analyzed. Based on the screening results, TRIM28 (tripartite motif-containing 28) expression was evaluated in ferroptotic cardiomyocytes. Cardiac I/R injury models in mice and hypoxia/reoxygenation injury models in neonatal rat ventricular myocytes were established. To explore the function of TRIM28, we used adeno-associated virus serotype 9 to achieve cardiomyocyte-specific overexpression and generated tamoxifen-inducible cardiomyocyte-specific TRIM28 knockout mice. RNA sequencing, coimmunoprecipitation coupled with mass spectrometry, and ubiquitinome profiling were applied to elucidate the underlying mechanisms. Human heart samples from patients with ischemic heart disease were used to evaluate the expression of TRIM28 and its related signaling molecules. The Connectivity Map database was used to screen potential activators of TRIM28.
resultsWe found that TRIM28 expression was downregulated in ferroptosis inducer-treated and hypoxia/reoxygenation-injured cardiomyocytes, as well as in I/R-injured mouse hearts. Cardiomyocyte-specific overexpression of TRIM28 protected the heart against I/R-induced ferroptosis, whereas its deficiency exacerbated myocardial I/R-induced ferroptotic injury. Mechanistically, TRIM28 functioned as an E3 ubiquitin ligase that directly bound to IRP2 (iron regulatory protein 2) and promoted K48-linked ubiquitination at the K877 site, leading to the downregulation of IRP2 and TFR1 (transferrin receptor 1), suppression of intracellular iron uptake, and consequent attenuation of cardiomyocyte ferroptosis. Furthermore, p55γ interacted with and upregulated TRIM28, thereby mitigating I/R-induced myocardial ferroptosis. Consistent with these findings, protein levels of TRIM28 and p55γ were decreased in heart samples from patients with ischemic heart disease, whereas IRP2 and TFR1 were increased. Last, we demonstrated that perhexiline inhibited I/R-induced myocardial ferroptosis by upregulating p55γ and TRIM28.
conclusionsOur study identifies TRIM28 as an essential E3 ubiquitin ligase of IRP2 and delineates that TRIM28-mediated inhibition of myocardial ferroptosis by targeting IRP2-TFR1 signaling protects the heart against I/R injury, indicating that targeting TRIM28 represents a promising therapeutic strategy for suppressing cardiomyocyte ferroptosis and I/R injury.
Indexed as
FerroptosisMyocardial Reperfusion InjuryMyocytes, CardiacTripartite Motif-Containing Protein 28Ubiquitin-Protein LigasesAnimalsHumansMaleMiceMice, Inbred C57BLMice, KnockoutRatsRats, Sprague-DawleyTRIM28 protein, humanTripartite Motif-Containing Protein 28Ubiquitin-Protein LigasesferroptosisIRP2perhexilinereperfusion injuryTRIM28
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.
TRIM28 Is an E3 Ligase of IRP2 Suppressing Ischemia/Reperfusion-Induced Myocardial Ferroptosis. · full record | Socratic