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Title: Angiotensin-converting enzyme inhibition and food restriction in diabetic mice do not correct the increased sensitivity for ischemia-reperfusion injury
Authors: Van der Mieren, Gerry ×
Nevelsteen, Ines
Vanderper, Annelies
Oosterlinck, Wouter
Flameng, Willem
Herijgers, Paul #
Issue Date: 1-Aug-2012
Publisher: BioMed Central
Series Title: Cardiovascular Diabetology vol:11 pages:89-99
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.

CONCLUSION: 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.
ISSN: 1475-2840
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Experimental Cardiac Surgery
× corresponding author
# (joint) last author

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