Figure 7.

CSE-induced endothelial apoptosis proceeds according to a two-step mechanism. Cigarette smoke induces the up-regulation of CXCR3 on the surface of endothelial cells, which requires the generation of reactive oxygen species (ROS), which together with endothelial nitric oxide (NO) leads to the formation of peroxynitrite and protein nitration (PN), in parallel with the up-regulation of EMAP II. The concerted up-regulation of these two factors results in increased p38 mitogen-activated protein kinase–dependent apoptosis signaling through the CXCR3 receptor.