Overexpression of A1, an NF-κB–Inducible Anti-Apoptotic Bcl Gene, Inhibits Endothelial Cell Activation

Abstract

Abstract A1 is an anti-apoptotic bcl gene that is expressed in endothelial cells (EC) in response to pro-inflammatory stimuli. We show that in addition to protecting EC from apoptosis, A1 inhibits EC activation and its associated expression of pro-inflammatory proteins by inhibiting the transcription factor nuclear factor (NF)-κB. This new anti-inflammatory function gives a broader dimension to the protective role of A1 in EC. We also show that activation of NF-κB is essential for the expression of A1. Taken together, our data suggest that A1 downregulates not only the pro-apoptotic and pro-inflammatory response, but also its own expression, thus restoring a quiescent phenotype to EC.