title: Cardioprotective and anti-inflammatory effects of interleukin converting enzyme inhibition in experimental diabetic cardiomyopathy.
abstract: OBJECTIVE
  We investigated the effect of pharmacological inhibition of the interleukin converting enzyme (ICE) on cardiac inflammation, apoptosis, fibrosis, and left ventricular function in an animal model of diabetes.
  
  
  METHODS
  Diabetes was induced in 24 Sprague-Dawley rats by injection of streptozotozin (STZ) (70 mg/kg). Diabetic animals were treated with the interleukin converting enzyme (ICE) inhibitor (ICEI) (n = 12) or with a placebo (n = 12). Nondiabetic rats served as controls (n = 12). Left ventricular function was documented 6 weeks after induction of diabetes. Cardiac tissue was analyzed for the expression of cytokines, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, leukocyte and macrophage integrins, and collagen. Phosphorylation of Akt was analyzed by Western blot and apoptosis by Blc-2 and Bax measurements.
  
  
  RESULTS
  Left ventricular function was significantly impaired in diabetic animals. This was accompanied by a significant increase of cytokines, cell adhesion molecules, leukocytes 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.
  
  
  CONCLUSIONS
  Cardiac dysfunction is associated with cardiac inflammation in experimental diabetic cardiomyopathy. Both of these--cardiac dysfunction and inflammation--are attenuated after treatment with ICEI. These data suggest that anticytokine-based therapies might be beneficial in diabetic cardiomyopathy.
authors.affiliation: Department of Cardiology, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Westermann
authors.forename: Sophie
authors.initials: S
authors.lastname: Van Linthout
authors.forename: Sameer
authors.initials: S
authors.lastname: Dhayat
authors.forename: Nasser
authors.initials: N
authors.lastname: Dhayat
authors.forename: Felicitas
authors.initials: F
authors.lastname: Escher
authors.forename: Carola
authors.initials: C
authors.lastname: Bücker-Gärtner
authors.forename: Frank
authors.initials: F
authors.lastname: Spillmann
authors.forename: Michel
authors.initials: M
authors.lastname: Noutsias
authors.forename: Alexander
authors.initials: A
authors.lastname: Riad
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000276:immunology*; D020170:Caspase 1 / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D007249:Inflammation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D020170:Caspase 1