FIGURE 2.

Functional effects of bilirubin on endothelial cells. Positive loop between plasma- and HMOX1 derived bilirubin is shown highlighting the main activities in maintaining endothelial function. The ability to reduce oxidative stress by quenching both O₂^–. and ONOO^– prevents the dysfunction due to HG or AngII. The increased bioavailability of NO favors vascular relaxation and further activates HMOX1. The direct activity of bilirubin and HMOX1 in preventing the expression of adhesion molecules (VCAM, ICAM, E-selectin) is showed as well as the generation of angiogenetic factors (VEGF, IL-8, VEGF soluble receptor). A further contribution from VSMC-derived bilirubin has been hypothesized. References in brackets.