Lack of MG53 in human heart precludes utility as a biomarker of myocardial injury or endogenous cardioprotective factor

Cardiovascular Research
Frances A LemckertSandra T Cooper

Abstract

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. 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 mapp...Continue Reading

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Citations

Jan 8, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Xiaofei CongXiaoli Zhao
Nov 27, 2018·Cardiovascular Research·Heather Y Small, Tomasz J Guzik
Feb 12, 2019·Journal of the American Heart Association·T M Ayodele AdesanyaJianjie Ma
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Apr 20, 2020·Cardiology·Jing-Rui ZhangChang-Yi Li

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