Abstract 10713: Decrease in Oxidative Stress Associated with Hyperbilirubinemia and Augmentation of Endothelial Function in Gilbert Syndrome
Background: Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. Therefore, patients with Gilbert syndrome are ideal models for determining how endothelium-dependent vasodilation is affected by bilirubin-induced decrease in oxidative stress. We evaluated the role of oxidative stress in endothelial function in patients with Gilbert syndrome under normal conditions without cardiovascular risk factors.
Methods and results: A total of 108 young men with Gilbert syndrome without cardiovascular risk factors and 108 age-matched healthy men (normal controls) were enrolled in this study. Serum concentrations of bilirubin were higher in patients with Gilbert syndrome than in control subjects (29.2±11.6 vs. 9.4±2.7 µmol/L, P<0.001). Serum concentration of malondialdehyde-modified low-density lipoprotein (MDA-LDL) and urinary excretion of 8-hydroxy-2’-deoxyguanosine (8-OHdG), as indices of oxidative stress, were lower in patients with Gilbert syndrome than in control subjects (61.8±24.5 vs. 72.5±21.8 U/L, P=0.034, 7.8±2.4 vs. 10.4±3.2 ng/mg creatinine, P=0.001, respectively). Flow-mediated vasodilation (FMD) was greater in patients with Gilbert syndrome than in normal control subjects (7.2±2.2 vs. 5.9±1.7 %, P<0.001). Vascular responses to nitroglycerin were not significantly different between the two groups. FMD correlated with serum concentration of bilirubin (r=0.44, P<0.001), MDA-LDL (r=-0.25, P=0.01), and urinary excretion of 8-OHdG (r=-0.27, P=0.004) in patients with Gilbert syndrome but not in control subjects. In addition, serum concentration of bilirubin correlated with MDA-LDL (r=-0.20, P=0.04) and 8-OHdG (r=-0.21, P=0.02) in patients with Gilbert syndrome but not in control subjects.
Conclusion: Patients with Gilbert syndrome had low levels of oxidative stress associated with hyperbilirubinemia and enhancement of endothelium-dependent vasodilation.
- © 2012 by American Heart Association, Inc.