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
References
Jul 13, 2001·Journal of Molecular and Cellular Cardiology·N AskenasyD L Farkas
Dec 2, 2008·Nature Cell Biology·Chuanxi CaiJianjie Ma
Apr 22, 2009·The Journal of Thoracic and Cardiovascular Surgery·Jonathan R EganDavid S Winlaw
May 15, 2010·Circulation Research·Xianhua WangHeping Cheng
Jun 3, 2010·Circulation·Chun-Mei CaoRui-Ping Xiao
Jul 16, 2010·Physiological Genomics·Matthew S BarnabeiJoseph M Metzger
Feb 3, 2011·Cardiovascular Research·Yan ZhangRui-Ping Xiao
Mar 18, 2011·Journal of Neuropathology and Experimental Neurology·Leigh B WaddellSandra T Cooper
Jun 23, 2012·Science Translational Medicine·Noah WeislederJianjie Ma
Mar 22, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Angela LekSandra T Cooper
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Dec 24, 2013·Journal of Molecular and Cellular Cardiology·Joshua J Martindale, Joseph M Metzger
Feb 28, 2014·Journal of the American Heart Association·Huei-Ping TzengDouglas L Mann
Dec 24, 2014·Journal of Molecular and Cellular Cardiology·Jianxun LiuJianjie Ma
Feb 7, 2015·Journal of Molecular and Cellular Cardiology·Mark J Kohr
Citations
May 13, 2017·PloS One·Yasuhiro IchikawaDavid M Roth
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
Dec 28, 2018·Circulation·Hong-Kun WuRui-Ping Xiao
Feb 12, 2019·Journal of the American Heart Association·T M Ayodele AdesanyaJianjie Ma
Apr 23, 2017·Molecular Pharmacology·Yan ZhangRui-Ping Xiao
Aug 6, 2019·Circulation·Hua ZhuBryan A Whitson
Feb 29, 2020·Cells·Anna V Bulankina, Sven Thoms
Jul 21, 2020·The Journal of Clinical Investigation·Kevin E McElhanonNoah Weisleder
Apr 10, 2020·PloS One·Brian J PaleoNoah Weisleder
Feb 26, 2020·Cancers·Hiroko Ishiwata-EndoJoel Moss
Jun 24, 2020·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Julia HofhuisSven Thoms
Nov 5, 2016·The Journal of Biological Chemistry·Hyun LeeYoung-Gyu Ko
Mar 2, 2019·Journal of Cellular Physiology·Xu ChenQijun Zheng
Jul 18, 2020·Circulation·Dan ShanRui-Ping Xiao
Jun 10, 2018·Experimental & Molecular Medicine·Jun Sub ParkYoung-Gyu Ko
Mar 11, 2019·Pathology Oncology Research : POR·M J Fernández-AceñeroA Cebrián
Sep 29, 2019·International Journal of Molecular Sciences·Andrea BaehrChristian Kupatt
Oct 3, 2020·Cardiovascular Toxicology·Wenhua JiangHeng Ma
Nov 16, 2016·Journal of Diabetes Research·Jie QiJun Zhang
May 29, 2018·The Tohoku Journal of Experimental Medicine·Zhuoyu ChenYurong Qiu
Jan 5, 2021·Frontiers in Physiology·Hongyang XieXiaoxiang Yan
Feb 11, 2021·PloS One·Clothilde PhilouzePhilippe Delerive
Jan 15, 2021·Cells·Zhongguang LiJianjie Ma
Mar 22, 2021·Molecular Biology and Evolution·Yuanqing FengRui-Ping Xiao
Jun 30, 2021·Cell & Bioscience·Weina ZhongPeter H U Lee
Apr 20, 2020·Cardiology·Jing-Rui ZhangChang-Yi Li