| Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. | |
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MedLine Citation:
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PMID: 23426181 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Min Luo; Xiaoqun Guan; Elizabeth D Luczak; Di Lang; William Kutschke; Zhan Gao; Jinying Yang; Patric Glynn; Samuel Sossalla; Paari D Swaminathan; Robert M Weiss; Baoli Yang; Adam G Rokita; Lars S Maier; Igor R Efimov; Thomas J Hund; Mark E Anderson |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-2-15 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: - ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-2-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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