The present inventors discovered that PKCε is necessary for VEGF signaling through PI3K/Akt-dependent pathways and is involved in MAPK-dependent pathways, thus regulating eNOS activity and DNA synthesis, respectively. Thus differential manipulation of PKCε activity can be used to modify VEGF effects in conditions in which modulation of angiogenesis is desirable (e.g., for treatment of diabetic proliferative retinopathy or to enhance angiogenesis for treatment of peripheral and myocardial ischemia).