Diabetes increases mortality after myocardial infarction by oxidizing CaMKII

2013 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Diabetes increases mortality after myocardial infarction by oxidizing CaMKII​
Luo, M.; Guan, X.; Luczak, E. D.; Lang, D.; Kutschke, W.; Gao, Z. & Yang, J. et al.​ (2013) 
Journal of Clinical Investigation123(3) pp. 1262​-1274​.​ DOI: https://doi.org/10.1172/JCI65268 

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Authors
Luo, Min; Guan, Xiaoqun; Luczak, Elizabeth D.; Lang, Di; Kutschke, William; Gao, Zhan; Yang, Jinying; Glynn, Patric; Sossalla, Samuel ; Swaminathan, Paari D.; Weiss, Robert M.; Yang, Baoli; Rokita, Adam G.; Maier, Lars S. ; Efimov, Igor R.; Hund, Thomas J.; Anderson, Mark E.
Abstract
Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction. Streptozotocin-treated mice had increased pacemaker cell ox-CaMKII and apoptosis, which were further enhanced by myocardial infarction. We developed a knockin mouse model of oxidation-resistant CaMKII delta (MM-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. Our findings suggest that activation of a mitochondrial/ox-CaMKII pathway contributes to increased sudden death in diabetic patients after myocardial infarction.
Issue Date
2013
Journal
Journal of Clinical Investigation 
Project
SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz 
SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz 
Working Group
RG L. Maier (Experimentelle Kardiologie) 
RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung) 
External URL
https://sfb1002.med.uni-goettingen.de/production/literature/publications/105
ISSN
0021-9738
Language
English

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