Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy.
BACKGROUND
Insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGFbeta) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy.


METHODS
Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFbeta and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs.


RESULTS
Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFbeta, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression.


CONCLUSIONS
These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies.
Mahmoudabady
Maryam
M
Laboratory of Physiology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. maryam.mamoudabadi@ulb.ac.be
Mathieu
Myrielle
M
Touihri
Karim
K
Hadad
Ielham
I
Da Costa
Agnes Mendes
AM
Naeije
Robert
R
Mc Entee
Kathleen
K
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism
D016213:Cyclins; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1