Insulin-like growth factor I improves cardiovascular function and suppresses apoptosis of cardiomyocytes in dilated cardiomyopathy

To investigate how insulin-like growth factor I (IGF-I) modulates cardiovas cular function and myocardial apoptosis in heart failure, the therapeutic e ffects of IGF-I were determined in a canine model of dilated cardiomyopathy . The animals were paced at 220 beats/min, and the left ventricular (LV) ch amber became dilated after 2 weeks. A subset of paced dogs was treated with sc injections of IGF-I from week 3 to week 4. After 4 weeks of pacing, unt reated paced dogs developed significant ventricular dysfunction. IGF-I-trea ted paced dogs showed better cardiac output, stroke volume, LV end-systolic pressure, and LV end-diastolic pressure. Moreover, pulmonary wedge pressur e and systemic vascular resistance were increased in the untreated group an d decreased in the IGF I-treated group. IGF-I treatment was associated with less thinning of the ventricular wall. Compared with the controls, untreat ed paced dogs showed increased apoptosis of cardiac muscle cells, which was partially suppressed by IGF-I treatment. The myocardial apoptotic index wa s negatively related to the thickness of the ventricular wall and to cardia c output, suggesting that ventricular remodeling/dysfunction involves the o ccurrence of myocardial apoptosis. Due to the close resemblance between thi s experimental model of dilated cardiomyopathy and human heart failure, the results of this study provide evidence that IGF-I may be a potential thera peutic agent for the failing human heart.