Hyperbilirubinemia, Augmentation of Endothelial Function, and Decrease in Oxidative Stress in Gilbert Syndrome

被引：93

作者：

Maruhashi, Tatsuya ^{[2
]}

Soga, Junko ^{[2
]}

Fujimura, Noritaka ^{[2
]}

Idei, Naomi ^{[2
]}

Mikami, Shinsuke ^{[2
]}

Iwamoto, Yumiko ^{[2
]}

Kajikawa, Masato ^{[2
]}

Matsumoto, Takeshi ^{[2
]}

Kihara, Yasuki ^{[2
]}

Chayama, Kazuaki ^{[3
]}

Noma, Kensuke

Nakashima, Ayumu ^{[4
]}

Tomiyama, Hirofumi ^{[5
]}

Takase, Bonpei ^{[6
]}

Yamashina, Akira ^{[5
]}

Higashi, Yukihito ^{[1
,4
]}

机构：

[1] Hiroshima Univ, Dept Cardiovasc Regenerat & Med, Res Inst Radiat Biol & Med, Minami Ku, Hiroshima 7348551, Japan

[2] Hiroshima Univ, Dept Cardiovasc Med, Grad Sch Biomed Sci, Hiroshima 7348551, Japan

[3] Hiroshima Univ, Dept Med & Mol Sci, Grad Sch Biomed Sci, Hiroshima 7348551, Japan

[4] Hiroshima Univ Hosp, Div Regenerat & Med, Hiroshima, Japan

[5] Tokyo Med Univ, Dept Internal Med 2, Tokyo, Japan

[6] Natl Def Med Coll, Res Inst, Div Biomed Engn, Tokorozawa, Saitama 359, Japan

来源：

CIRCULATION | 2012年 / 126卷 / 05期

关键词：

bilirubin; endothelial function; oxidative stress; peripheral vascular diseases; Gilbert syndrome; MALONDIALDEHYDE-MODIFIED LDL; BILIRUBIN; ACTIVATION; DISEASE; DYSFUNCTION; OXIDASE; RISK; ANGIOTENSIN; PREVALENCE; MECHANISMS;

D O I：

10.1161/CIRCULATIONAHA.112.105775

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. 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 versus 9.4 +/- 2.7 mu mol/L; P<0.001). Serum concentrations of malondialdehyde-modified low-density lipoprotein 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 versus 72.5 +/- 21.8 U/L, P=0.034; 7.8 +/- 2.4 versus 10.4 +/- 3.2 ng/mg creatinine, P=0.001, respectively). Flow-mediated vasodilation was greater in patients with Gilbert syndrome than in normal control subjects (7.2 +/- 2.2% versus 5.9 +/- 1.7%; P<0.001). Vascular responses to nitroglycerine were not significantly different between the 2 groups. Flow-mediated vasodilation correlated with serum concentration of bilirubin (r=0.44, P<0.001), malondialdehyde-modified low-density lipoprotein (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 malondialdehyde-modified low-density lipoprotein (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. Conclusions-Patients with Gilbert syndrome had low levels of oxidative stress associated with hyperbilirubinemia and enhancement of endothelium-dependent vasodilation.

引用

页码：598 / 603

页数：6

共 37 条

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