SIGNALING PATHWAYS THAT CONTROL ANGIOGENESIS, GROWTH AND FUNCTION IN THE HEART

The phosphatidylinositol-3 kinase (PI3K)-Akt signaling axis mediates cellular growth responses in multiple organisms and cell types. In endothelial cells, it is activated by many angiogenic growth factors and regulates downstream target molecules that are involved in blood vessel growth and homeostasis. In the heart, this signaling cascade is an important positive regulator of post-natal cardiac growth, and it is activated in diseases that increase heart weight relative to body weight. Heart failure is a final common consequence of various heart diseases, and is a leading cause of mortality worldwide. Hypertrophy of cardiac muscle cells is a common feature of failing myocardium. Cardiac myocyte hypertrophy is initially an adaptive response to increased external load that occurs in pathological situations because it can normalize the increase in wall stress induced by mechanical overload. However, increased cardiac mass can also lead to dilated cardiomyopathy (heart failure) through poorly understood mechanisms. Thus, stress-induced or ‘pathological ’ cardiac hypertrophy appears to be detrimental for the heart, at least in the chronic phase. On the other hand, normal post-natal growth of the heart or exercise-induced cardiac growth also occurs through hypertrophy of individual cardiac muscle cells. These forms of so called ‘physiological ’ cardiac hypertrophy are not associated with contractil