OVEREXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I IN MICE PROTECTS FROM MYOCYTE DEATH AFTER INFARCTION, ATTENUATING VENTRICULAR DILATION, WALLSTRESS, AND CARDIAC-HYPERTROPHY

To determine whether IGF-1 opposes the stimulation of myocyte death in the surviving myocardium after infarction, transgenic mice overexpres sing human IGF-1B in myocytes (FVB.Igf+/-) and wild-type littermates a t 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 in farction, myocyte apoptosis increased 4.2-fold and 2.1-fold in nontran sgenics at 1.5 and 2.5 mo, respectively, Corresponding increases in my ocyte 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 a ge after infarction. In 2.5-mo-old infarcted nontransgenics, functiona l 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 cavi tary 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, c ardiac weight, and left and right ventricular weight-to-body wt ratios . In conclusion, constitutive overexpression of IGF-1 prevented activa tion of cell death in the viable myocardium after infarction, limiting ventricular dilation, myocardial loading, and cardiac hypertrophy.