Lack of MG53 in Human Heart Precludes Utility As a Biomarker of Myocardial Injury or Endogenous Cardioprotective Factor

Overview

Journal Cardiovasc Res

Specialty Cardiology & Vascular Diseases

Date 2016 Jan 22

PMID 26790476

Citations 27

Authors

Frances A Lemckert

Adam Bournazos

Daniel M Eckert

Manuel Kenzler

Joanne M Hawkes

Tanya L Butler

Bradley Ceely

Kathryn N North

David S Winlaw

Jonathan R Egan

Sandra T Cooper

Affiliations

Soon will be listed here.

Abstract

Aims: Mitsugumin-53 (MG53/TRIM72) is an E3-ubiquitin ligase that rapidly accumulates at sites of membrane injury and plays an important role in membrane repair of skeletal and cardiac muscle. MG53 has been implicated in cardiac ischaemia-reperfusion injury, and serum MG53 provides a biomarker of skeletal muscle injury in the mdx mouse model of Duchenne muscular dystrophy. We evaluated the clinical utility of MG53 as a biomarker of myocardial injury.

Methods And Results: We performed Langendorff ischaemia-reperfusion injury on wild-type and dysferlin-null murine hearts, using dysferlin deficiency to effectively model more severe outcomes from cardiac ischaemia-reperfusion injury. MG53 released into the coronary effluent correlated strongly and significantly (r = 0.79-0.85, P < 0.0001) with functional impairment after ischaemic injury. We initiated a clinical trial in paediatric patients undergoing corrective heart surgery, the first study of MG53 release with myocardial injury in humans. Unexpectedly, we reveal although MG53 is robustly expressed in rat and mouse hearts, MG53 is scant to absent in human, ovine, or porcine hearts. Absence of MG53 in 11 human heart specimens was confirmed using three separate antibodies to MG53, each subject to epitope mapping and confirmed immunospecificity using MG53-deficient muscle cells.

Conclusion: MG53 is an effective biomarker of myocardial injury and dysfunction in murine hearts. However, MG53 is not expressed in human heart and therefore does not hold utility as a clinical biomarker of myocardial injury. Although cardioprotective roles for endogenous myocardial MG53 cannot be extrapolated from rodents to humans, potential therapeutic application of recombinant MG53 for myocardial membrane injury prevails.

Citing Articles

Advances in the Study of MG53 in Cardiovascular Disease.

Liu S, Zhao Q, Li W, Zhao J Int J Gen Med. 2023; 16:6073-6082.

PMID: 38152078 PMC: 10752033. DOI: 10.2147/IJGM.S435030.

Structural basis for TRIM72 oligomerization during membrane damage repair.

Ma Y, Ding L, Li Z, Zhou C Nat Commun. 2023; 14(1):1555.

PMID: 36944613 PMC: 10030467. DOI: 10.1038/s41467-023-37198-1.

Protective role of MG53 against ischemia/reperfusion injury on multiple organs: A narrative review.

Xu B, Wang C, Chen H, Zhang L, Gong L, Zhong L Front Physiol. 2022; 13:1018971.

PMID: 36479346 PMC: 9720843. DOI: 10.3389/fphys.2022.1018971.

Blocking MG53 Phosphorylation Protects Diabetic Heart From Ischemic Injury.

Lv F, Wang Y, Shan D, Guo S, Chen G, Jin L Circ Res. 2022; 131(12):962-976.

PMID: 36337049 PMC: 9770150. DOI: 10.1161/CIRCRESAHA.122.321055.

MG53 Inhibits Necroptosis Through Ubiquitination-Dependent RIPK1 Degradation for Cardiac Protection Following Ischemia/Reperfusion Injury.

Wang Q, Park K, Geng B, Chen P, Yang C, Jiang Q Front Cardiovasc Med. 2022; 9:868632.

PMID: 35711363 PMC: 9193967. DOI: 10.3389/fcvm.2022.868632.

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