The valosin-containing protein promotes cardiac survival through the inducible isoform of nitric oxide synthase

Expression of the heat shock protein 22 (Hsp22) in the heart stimulates cardiac cell survival through activation of the Akt pathway and expression of the inducible nitric oxide (NO) synthase (iNOS), the mediator of ischaemic preconditioning and the most powerful prophylaxis against cardiac cell death. The goal of the present study was to elucidate the downstream effector by which Hsp22 and Akt increase iNOS expression. We tested both in vivo and in vitro the hypothesis that such an effector is the valosin-containing protein (VCP), an Akt substrate, which activates the transcription factor NF-κB, using a transgenic mouse with cardiac-specific over-expression of Hsp22, as well as isolated rat cardiac myocytes.