Modulation of endothelial cell apoptosis by heme oxygenase-1-derived carbon monoxide.

It is well established that expression of heme oxygenase-1 (HO-1) acts in a cytoprotective manner in a variety of cell types, including in endothelial cells (EC). We have recently shown that HO-1 expression protects EC from undergoing apoptosis. We have also shown that the antiapoptotic effect of HO-1 is mediated through heme catabolism into the gas carbon monoxide (CO). In this review, we discuss the possible molecular mechanisms by which HO-1-derived CO suppresses EC apoptosis. We will review data suggesting that the antiapoptotic effect of CO acts through the activation of the p38 mitogen-activated protein kinase signal transduction pathway and requires the activation of the transcription factor nuclear factor-kappa B (NF-kappa B), as well as the expression of a subset of NF-kappa B-dependent antiapoptotic genes.