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Cardiovascular Research 2001 50(3):516-524; doi:10.1016/S0008-6363(01)00237-1
© 2001 by European Society of Cardiology
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Copyright © 2001, European Society of Cardiology

Cardiac remodeling after myocardial infarction is impaired in IGF-1 deficient mice

M. Palmena, M.J.A.P. Daemenc, R. Bronsaera, W.R.M. Dassena, H.R. Zandbergena, M. Kockxd, J.F.M. Smitsb, R. van der Zeea and P.A. Doevendansa,*

aDepartment of Cardiology, Cardiovascular Research Institute, Maastricht, University of Maastricht, The Netherlands
bDepartment of Pharmacology, Cardiovascular Research Institute, Maastricht, University of Maastricht, The Netherlands
cDepartment of Pathology, Cardiovascular Research Institute, Maastricht, University of Maastricht, The Netherlands
dDepartment of Pathology, APCAM, AZ Middelheim, Antwerp, Belgium

* Corresponding author. Department of Cardiology, Academic Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands. Tel.: +31-43-387-5095; fax: +31-43-387-5104 p.doevendans{at}cardio.azm.nl

Objective: To obtain more insight in the role of IGF-1 in cardiac remodeling and function after experimental myocardial infarction. We hypothesized that cardiac remodeling is altered in IGF-1 deficient mice, which may affect cardiac function. Methods: A myocardial infarction was induced by surgical coronary artery ligation in heterozygous IGF-1 deficient mice. One week after surgery, left ventricular function was analyzed, and parameters of cardiac remodeling were measured. Results: No significant difference in cardiac function was found between infarcted wildtype and knock-out animals, despite a marked reduction in capillarization and blunting of the hypertrophic response of the interventricular septum in the IGF-1 deficient group. Furthermore, decreased DNA synthesis and increased apoptosis rates were observed in the IGF-1 knock-out mice. Conclusion: IGF-1 deficient mice show preservation of cardiac function 1 week after MI, despite an altered cardiac remodeling process.

KEYWORDS BrdU, 5-Bromo-deoxyuridine; BW, Body weight; CD, Capillary density; C/F ratio, Capillary to fiber ratio; GH, Growth hormone; HW, Heart weight; HR, Heart rate; HZ, Heterozygous (IGF-1+/–); IGF-1, Insulin-like growth factor-1; IGF-1R, IGF-1 receptor; IGF-2, Insulin-like growth factor-2; LVEDP, Left ventricular end diastolic pressure; LVFW, Left Ventricular Free Wall; MD, Myocyte density; MI, Myocardial infarction; PBS, Phosphate Buffered Saline; +dP/dt, Maximal rate of positive pressure development (contractility); –dP/dt, Maximal rate of negative pressure development (relaxation); SLVP, Systolic left ventricular pressure; TLF, Total Labeling Fraction; TUNEL, Terminal Transferase dUTP Nick End Labeling; WT, Wildtype (non-transgenic littermate)


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