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Activation of protective and damaging components of the cardiac renin-angiotensin system after myocardial infarction in experimental diabetes

Minerva Foundation Institute for Medical Research, Biomedicum, Helsinki, Haartmaninkatu 8, FIN-00029 Helsinki, Finland, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

Päivi Lakkisto

Minerva Foundation Institute for Medical Research, Biomedicum, Helsinki, Haartmaninkatu 8, FIN-00029 Helsinki, Finland, Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland

Eeva Palojoki

Minerva Foundation Institute for Medical Research, Biomedicum, Helsinki, Haartmaninkatu 8, FIN-00029 Helsinki, Finland, Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland

Tina Grönholm

Minerva Foundation Institute for Medical Research, Biomedicum, Helsinki, Haartmaninkatu 8, FIN-00029 Helsinki, Finland, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

Antti Saraste

Department of Anatomy, University of Turku, Turku, Finland

Piet Finckenberg

Institute of Biomedicine, Pharmacology, University of Helsinki, Biomedicum Helsinki, Finland

Eero Mervaala

Institute of Biomedicine, Pharmacology, University of Helsinki, Biomedicum Helsinki, Finland

Ilkka Tikkanen

Minerva Foundation Institute for Medical Research, Biomedicum, Helsinki, Haartmaninkatu 8, FIN-00029 Helsinki, Finland, ilkka.tikkanen{at}helsinki.fi, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

Mika Laine

Minerva Foundation Institute for Medical Research, Biomedicum, Helsinki, Haartmaninkatu 8, FIN-00029 Helsinki, Finland, Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland

Introduction. Diabetes is associated with prolonged apoptotic cell death of cardiac myocytes and adverse remodelling after myocardial infarction (MI). Because the renin-angiotensin system (RAS) has a major role in the remodelling, we studied whether diabetes is associated with altered regulation of RAS after MI in rats.

Methods. Male Wistar rats were randomised to receive either streptozotocin (diabetic group) or citrate buffer (control group) intravenously. MI was produced four weeks later by ligating the left descending coronary artery.The rats were sacrificed 1, 4 and 12 weeks after the operation. Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE 2), angiotensin type 1 and 2 receptors (AT₁-receptor, AT₂-receptor), and connective tissue growth factor (CTGF) mRNA expression were determined.

Results. The expression of both protective and damaging components of RAS increased after MI. However, myocardial ACE 2 and AT₂-receptor messenger ribonucleic acid (mRNA) expression levels were significantly lower in diabetic compared to non-diabetic rats 1 week after MI. In contrast, AT₁-receptor, ACE and CTGF mRNA levels were up-regulated in diabetic as compared with non-diabetic rats 12 weeks after MI.

Conclusion. The activation of the protective components of RAS (ACE 2 and AT2-receptor) was blunted early after MI in diabetic rats, whereas the levels of ACE, AT₁-receptor and CTGF mRNA leading to adverse effects on myocardium, were elevated in diabetic as compared with non-diabetic rats.This unbalanced activation of the RAS may influence the pathophysiology of myocardial injury in diabetes after MI.

Key Words: renin-angiotensin system • myocardial infarction • diabetes

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 8, No. 2, 66-73 (2007)
DOI: 10.3317/jraas.2007.018


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