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Title: Upregulation of cardiac insulin-like growth factor-I receptor by ACE inhibition after myocardial infarction: potential role in remodeling.
Authors: Dean, Rachael G;Bach, Leon A;Burrell, Louise M
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Australia.
Issue Date: 1-Jun-2003
Citation: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society; 51(6): 831-9
Abstract: This study evaluated the effects of angiotensin-converting enzyme (ACE) inhibition after myocardial infarction (MI) on cardiac remodeling and gene expression and localization of components (ligands, receptors, and binding proteins) of the cardiac insulin-like growth factor (IGF) system. After ligation of the coronary artery, rats were randomized to vehicle or ACE inhibitor (Captopril, 50 mg/kg/day) for 4 weeks. Blood pressure, cardiac remodeling, and components of the IGF system were localized in the heart using in situ hybridization (ISH) and immunohistochemistry (IHC). The average infarct size was 42%. There were regional differences in the expression of the IGF system after MI, with increased IGF-I mRNA abundance in the border (24-fold) and infarct (12-fold) and increased IGF-binding protein (IGFBP)-3 mRNA in all areas of the failing left ventricle (threefold). Captopril reduced blood pressure, attenuated cardiac remodeling, and caused a threefold increase in IGF-I receptor mRNA and protein in infarct, border zone, and viable myocardium (p<0.01). Captopril had no effect on IGF-I mRNA but further increased IGFBP-3 mRNA and protein in the border zone, (p<0.05). The changes in the cardiac IGF system following MI are highly localized, persist for at least 4 weeks, and can be modulated by ACE inhibition. These data suggest that the benefits of ACE inhibitors in attenuation of cardiac remodeling may be mediated in part through increased expression of the IGF-I receptor sensitizing the myocardium to the positive effects of endogenous IGF-I.
Internal ID Number: 12754294
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.pharmacology
Blood Pressure.drug effects
Insulin-Like Growth Factor Binding Protein 1.biosynthesis.genetics
Insulin-Like Growth Factor Binding Protein 2.biosynthesis.genetics
Insulin-Like Growth Factor Binding Protein 3.biosynthesis.genetics
Insulin-Like Growth Factor I.biosynthesis.genetics
Insulin-Like Growth Factor II.biosynthesis.genetics
Myocardial Infarction.metabolism.pathology.physiopathology
RNA, Messenger.biosynthesis
Rats, Sprague-Dawley
Receptor, IGF Type 1.biosynthesis
Ventricular Remodeling.drug effects
Appears in Collections:Journal articles

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