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Increased susceptibility to myocardial ischemia and reperfusion injury in type I diabetes mellitus is mannose‐binding lectin dependent
Author(s) -
Busche Marc Nicolai,
Walsh Mary C.,
Stahl Gregory L.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a11
Subject(s) - medicine , mannan binding lectin , diabetes mellitus , myocardial infarction , complement system , streptozotocin , troponin t , endocrinology , ischemia , lectin pathway , troponin , lectin , classical complement pathway , immunology , antibody
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