Apop-1 is a novel protein identified in cultured atherosclerotic smooth muscle cells of ApoE-deficient mice, and the expression of the Apop-1 protein induces the death of cultured cells. Insulin-like growth factor-1 (IGF-1) is a well-characterized survival factor for VSMC; however, the interaction between Apop-1 and survival factor IGF-1 ill the mediation of cell death is poorly understood. In this report, we show that the IGF-1 signaling cascade Protects VSMC against Apop-1-induced death. Furthermore, our data indicate that the inhibition of Apop-1-induced death by IGF-1 is mediated by the activation of the PI3K/Akt signaling pathway. (C) 2008 Elsevier Inc. All rights reserved.