Prostacyclin signaling boosts NADPH oxidase 4 in the endothelium promoting cytoprotection and angiogenesis

Abstract

Aims: Prostacyclin (PGI2) that is released from the vascular endothelium plays an important role in vasodilatation and thrombo-resistance, and it has long been suspected to protect cell survival. How it does so has never been clear. Recently, it has been shown that the NADPH oxidase 4 (Nox4) improves endothelial cell functions and promotes angiogenesis in vivo, but it was not known how to boost Nox4 therapeutically to exploit its protective functions in the vasculature. Here, we identified such a stimulus. Results: The selective and stable prostacyclin receptor (IP-R) agonist cicaprost increases the expression of Nox4 in human endothelial cells of several types, including endothelial progeni..