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01.12.2012 | Original investigation | Ausgabe 1/2012 Open Access

Cardiovascular Diabetology 1/2012

Angiotensin-converting enzyme inhibition and food restriction in diabetic mice do not correct the increased sensitivity for ischemia-reperfusion injury

Zeitschrift:
Cardiovascular Diabetology > Ausgabe 1/2012
Autoren:
Gerry Van der Mieren, Ines Nevelsteen, Annelies Vanderper, Wouter Oosterlinck, Willem Flameng, Paul Herijgers
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2840-11-89) contains supplementary material, which is available to authorized users.

Competing interest

The authors declare that they have no competing interests.

Authors’ contribution

GVDM carried out the mice breeding, treatments, biochemical analysis, PV-loop experiments and infarct size determination, data and statistical analysis, and drafted the manuscript. IN, AV and WO contributed to mice breeding, treatments and biochemical analysis. WF participated in the design of the study and general supervision. PH designed the study, obtained funding, did supervision of the analysis and interpretation of data, and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

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.
Zusatzmaterial
Authors’ original file for figure 1
12933_2012_506_MOESM1_ESM.pdf
Authors’ original file for figure 2
12933_2012_506_MOESM2_ESM.pdf
Literatur
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