Apoptosis and the cardiac action of insulin-like growth factor I

In both cardiac surgical and cardiological settings, clinical interventions used to reperfuse the ischemic heart are associated with myocardial damage that is likely to influence long-term functional recovery. Ischaemia and reperfusion trigger cardiomyocyte death by necrosis and apoptosis. Therefore identifying potent cardioprotective agents remains an important goal in cardiac research. In a variety of tissues, insulin-like growth factor I (IGF-I) stimulates cellular proliferation, somatic growth, and differentiation. In addition, IGF-I inhibits apoptotic cell death and therefore plays an important role as a cell survival factor. This characteristic would provide an opportunity to both protect (rescue) the cardiac myocytes during (after) cardiac insults. In this review, we shall (i) describe the characteristics of apoptotic cell death with particular emphasis on the heart, (ii) discuss the IGF system with emphasis on the cardiac actions of IGF-I under normal and pathological conditions, (iii) elaborate on the potential role of IGF-I in myocardial protection, and finally (iv) describe how an improved understanding of the cardiac actions of IGF-I may lead to better protective clinical strategies in the future. We discuss work by ourselves and others in these areas and also consider recent work describing the cellular signaling associated with the IGF-I receptor (IGF-IR) in the heart and its potential role in regulating excitation-contraction coupling.