title: Angiotensin-converting enzyme inhibition and food restriction in diabetic mice do not correct the increased sensitivity for ischemia-reperfusion injury.
abstract: BACKGROUND
  The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On top of their diabetic cardiomyopathy, these patients experience frequent and severe cardiac ischemia-reperfusion (IR) insults, which further aggravate their degree of heart failure. Food restriction and angiotensin-converting enzyme inhibition (ACE-I) are standard therapies in these patients but the effects on cardiac IR injury have never been investigated. In this study, we tested the hypothesis that 1° food restriction and 2° ACE-I reduce infarct size and preserve cardiac contractility after IR injury in mouse models of diabetes and the metabolic syndrome.
  
  
  METHODS
  C57Bl6/J wild type (WT) mice, leptin deficient ob/ob (model for type II diabetes) and double knock-out (LDLR-/-;ob/ob, further called DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome) were used. The effects of 12 weeks food restriction or ACE-I on infarct size and load-independent left ventricular contractility after 30 min regional cardiac ischemia were investigated. Differences between groups were analyzed for statistical significance by Student's t-test or factorial ANOVA followed by a Fisher's LSD post hoc test.
  
  
  RESULTS
  Infarct size was larger in ob/ob and DKO versus WT. Twelve weeks of ACE-I improved pre-ischemic left ventricular contractility in ob/ob and DKO. Twelve weeks of food restriction, with a weight reduction of 35-40%, or ACE-I did not reduce the effect of IR.
  
  
  CONCLUSIONS
  ACE-I and food restriction do not correct the increased sensitivity for cardiac IR-injury in mouse models of type II diabetes and the metabolic syndrome.
authors.affiliation: Department of Cardiovascular Sciences, Research Unit Experimental Cardiac Surgery, K.U. Leuven, Herestraat 49, B-3000, Leuven, Belgium.
authors.forename: Gerry
authors.initials: G
authors.lastname: Van der Mieren
authors.forename: Ines
authors.initials: I
authors.lastname: Nevelsteen
authors.forename: Annelies
authors.initials: A
authors.lastname: Vanderper
authors.forename: Wouter
authors.initials: W
authors.lastname: Oosterlinck
authors.forename: Willem
authors.initials: W
authors.lastname: Flameng
authors.forename: Paul
authors.initials: P
authors.lastname: Herijgers
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000235:genetics; D004195:Disease Models, Animal; D020738:Leptin / Q000172:deficiency / Q000235:genetics; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D020738:Leptin; D011973:Receptors, LDL