Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy.
To determine whether IGF-1 opposes the stimulation of myocyte death in the surviving myocardium after infarction, transgenic mice overexpressing human IGF-1B in myocytes (FVB.Igf+/-) and wild-type littermates at 1.5 and 2.5 mo of age were subjected to coronary ligation and killed 7 d later. Myocardial infarction involved an average 50% of the left ventricle, and produced cardiac failure. In the region proximate to infarction, myocyte apoptosis increased 4. 2-fold and 2.1-fold in nontransgenics at 1.5 and 2.5 mo, respectively. Corresponding increases in myocyte necrosis were 1. 8-fold and 1.6-fold. In contrast, apoptotic and necrotic myocyte death did not increase in FVB.Igf+/- mice at either age after infarction. In 2.5-mo-old infarcted nontransgenics, functional impairment was associated with a 29% decrease in wall thickness, 43% increase in chamber diameter, and a 131% expansion in chamber volume. Conversely, the changes in wall thickness, chamber diameter, and cavitary volume were 41, 58, and 48% smaller in infarcted FVB.Igf+/- than in nontransgenics. The differential response to infarction of FVB.Igf+/- mice resulted in an attenuated increase in diastolic wall stress, cardiac weight, and left and right ventricular weight-to-body wt ratios. In conclusion, constitutive overexpression of IGF-1 prevented activation of cell death in the viable myocardium after infarction, limiting ventricular dilation, myocardial loading, and cardiac hypertrophy.
Li
Q
Q
Department of Medicine, New York Medical College, Valhalla, New York 10595, USA.
Li
B
B
Wang
X
X
Leri
A
A
Jana
K P
KP
Liu
Y
Y
Kajstura
J
J
Baserga
R
R
Anversa
P
P
D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects*; D003331:Coronary Vessels / Q000601:surgery; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000627:therapeutic use*; D008026:Ligation; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology; D011994:Recombinant Proteins / Q000096:biosynthesis; D012038:Regeneration / Q000187:drug effects; D018754:Ventricular Dysfunction / Q000517:prevention & control*
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I