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Diabetes increases mortality after myocardial infarction by oxidizing CaMKII
Journal article   Open access   Peer reviewed

Diabetes increases mortality after myocardial infarction by oxidizing CaMKII

Min Luo, Xiaoqun Guan, Elizabeth D Luczak, Di Lang, William J Kutschke, Zhan Gao, Jinying Yang, Patric Glynn, Samuel Sossalla, Paari D Swaminathan, …
The journal of clinical investigation, Vol.123(3), pp.1262-1274
05/01/2013
DOI: 10.1172/JCI65268
PMID: 23426181
url
https://doi.org/10.1172/JCI65268View
Published (Version of record) Open Access

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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 CaMKIIδ (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.
 Cardiovascular System Erratum Research Article

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