Proteasome inhibition 1 h following ischemia protects GRK2 and prevents malignant ventricular tachyarrhythmias and SCD in a model of myocardial infarction

American Journal of Physiology. Heart and Circulatory Physiology
Shijun HuangD C Kem

Abstract

Arrhythmia-prone epicardial border zone (EBZ) tissues demonstrate decreased G protein-coupled receptor kinase-2 (GRK2) activity and increased sensitivity to isoproterenol 6-24 h after coronary artery ligation in the dog. We previously demonstrated that the ischemia-mediated decrease in GRK2 in cardiac ischemic tissue was largely blocked by proteasome blockade initiated 1 h before the onset of ischemia, and this was associated with significant cardioprotection against malignant ventricular tachyarrhythmias. For application to clinical circumstances, it is desirable to determine whether a clinical window exists following the onset of ischemia for such a protective effect. The treatment of six dogs with the selective proteasome inhibitor bortezomib 1 h after the surgical induction of left coronary artery ischemia provided 80% (EBZ) and 42% (infarct) protection (by immunoblot) against the loss of GRK2 at 24 h. There was no significant increase of heat shock protein 70(72) in the EBZ of bortezomib-treated animals compared with control. There was a striking absence of rapid (>300 beats/min) and very rapid (>360 beats/min) ventricular triplets that is highly predictive of sudden cardiac deaths (SCDs) during electrocardiogram monitorin...Continue Reading

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Citations

Jul 1, 2009·Cardiovascular Research·Alexander KlossBurkhardt Dahlmann
Aug 18, 2009·Cardiovascular Research·Osamu TsukamotoMasafumi Kitakaze
Sep 12, 2009·Cardiovascular Research·Xichun Yu, David C Kem
Aug 30, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zheqing P CaiLewis C Becker
Dec 12, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Justine Calise, Saul R Powell
Aug 19, 2014·Antioxidants & Redox Signaling·Oliver Drews, Heinrich Taegtmeyer
Oct 16, 2013·Expert Opinion on Investigational Drugs·Apostolos N KandilisStamatios Theocharis
Dec 24, 2014·Journal of Molecular and Cellular Cardiology·Jianxun LiuJianjie Ma
Nov 24, 2017·Expert Opinion on Therapeutic Targets·Alessandro CannavoGiuseppe Rengo
Jul 13, 2018·Veterinary and Comparative Oncology·K PatatsosC J Hawkins
May 28, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Matthias Majetschak
May 22, 2009·American Journal of Physiology. Renal Physiology·Julia M HuberKathrin Eller
Jan 29, 2013·The Journal of Trauma and Acute Care Surgery·Harold H BachMatthias Majetschak
Jul 19, 2008·Biochimica Et Biophysica Acta·Giulia MeariniLucie Carrier

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