| First Author | Luo M | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 3 | Pages | 1262-74 |
| PubMed ID | 23426181 | Mgi Jnum | J:207291 |
| Mgi Id | MGI:5555934 | Doi | 10.1172/JCI65268 |
| Citation | Luo M, et al. (2013) Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J Clin Invest 123(3):1262-74 |
| abstractText | 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 Ca(2+)/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 CaMKIIdelta (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. |
