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Diabetes Publish Ahead of Print published online ahead of print May 16, 2007
DOI: 10.2337/db06-1662
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Original Research

Cardioprotective and anti inflammatory effects of interleukin converting enzyme inhibition in experimental diabetic cardiomyopathy

Dirk Westermann, MD1, Sophie Van Linthout, PhD1, Sameer Dhayat, MD1, Nasser Dhayat, MD1, Felicitas Escher, MD1, Carola Bücker-Gärtner1, Frank Spillmann, MD1, Michel Noutsias, MD1, Alexander Riad, MD1, Heinz-Peter Schultheiss, MD1, and Carsten Tschöpe, MD1

1Department of Cardiology and Pneumology, Charité, Universititätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

Correspondence: carsten.tschoepe{at}yahoo.com

We investigated the effect of pharmacological inhibition of the interleukin converting enzyme on cardiac inflammation, apoptosis, fibrosis, and left ventricular (LV) function in an animal model of diabetes mellitus.

Diabetes mellitus was induced in 24 Sprague-Dawley rats by injection of streptozotozin (STZ, 70mg/kg). Diabetic animals were treated with the interleukin converting enzyme inhibitor (ICEI) (STZICEI, n=12) or with a placebo (STZ, n=12). Non diabetic rats served as controls (SD, n=12). LV function was documented 6 weeks after induction of diabetes mellitus. Cardiac tissue was analyzed for the expression of cytokines, adhesion molecules ICAM-1 and VCAM-1, leukocyte and macrophage integrins, and collagen. Phosphorylation of AKT was analyzed by western blot and apoptosis by Blc-2 and Bax measurements.

LV function was significantly impaired in diabetic animals. This was accompanied by a significant increase of cytokines, CAMs, leucocytes and macrophages, and collagen content. In addition, the phosphorylation state of AKT was reduced. These changes were significantly attenuated in the diabetic group treated with ICEI.

Cardiac dysfunction is associated with cardiac inflammation in experimental diabetic cardiomyopathy. Both of these -- cardiac dysfunction and inflammation -- are attenuated after treatment with the ICE inhibitor. These data suggest that anti-cytokine based therapies might be beneficial in diabetic cardiomyopathy.


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Copyright © 2007 by the American Diabetes Association.