Increased susceptibility to myocardial ischemia and reperfusion injury in type I diabetes mellitus is mannose‐binding lectin dependent

Diabetic patients have an increased incidence of acute myocardial infarction and subsequent mortality. Mannose binding lectin (MBL)‐dependent activation of the lectin complement pathway has been shown to play a critical role in non‐diabetic myocardial ischemia‐reperfusion (MI/R) injury; therefore, we investigated the role of MBL in diabetic MI/R injury. In streptozotocin (STZ)‐induced type I diabetic mice, ejection fraction (EF) was decreased by 19% (p<0.001), serum troponin I levels were increased by 2.8 fold (p=0.002) and myocardial neutrophil infiltration was increased following MI/R with 15 min of ischemia as compared to non‐diabetic WT mice. Treatment with insulin prevented the diabetic mice from these MI/R associated injuries. These results demonstrate that hyperglycemia associated with type I diabetes mellitus leads to increased susceptibility to MI/R injury. Interestingly, type I diabetic MBL‐deficient mice were protected from MI/R injury compared to diabetic WT mice with EF of 79% versus 69% (p=0.001), serum troponin I of 6 ng/ml versus 20 ng/ml (p<0.05) and decreased myocardial neutrophil infiltration. These data demonstrate for the first time that activation of complement by the MBL‐dependent lectin pathway plays a critical role in diabetic MI/R injury. This project was supported by NIH HL56068, HL52886, HL79758 and DE017821