Regulation of ROS Production and Vascular Function by Carbon Monoxide
Figure 4
CO prevents inflammatory responses via inhibition of NF-B signaling pathway. (a) Inflammatory stimuli such as TNF- and LPS lead to activation of ECs, which in turn activate inflammatory signaling cascades. The association between TLR4 and MyD88 inhibits IB kinase activity, leading to NF-B activation via p65/p50 nuclear translocation in TNF--stimulated ECs. CO significantly reduces TNF--induced Nox-mediated ROS generation, NF-B activation and the expression of adhesion molecules such as ICAM-1, VCAM-1, and selectins. (b) Inflammatory stimuli induce (i) the recruitment of monocytes to the endothelium, thereby promoting their transmigration into the arterial intima, (ii) ECs apoptosis and (iii) VSMC proliferation. CO diminishes this inflammatory activation by reducing the expression of adhesion molecules, stimulating EC survival and inhibiting VSMC proliferation.
