Bilirubin and biliverdin treatment of atherosclerotic diseases

被引:90
作者
Oellinger, Robert
Yamashita, Kenichiro
Bilban, Martin
Erat, Anna
Kogler, Pamela
Thomas, Michael
Csizmadia, Eva
Usheva, Anny
Margreiter, Raimund
Bach, Fritz H.
机构
[1] Univ Innsbruck, Dept Surg, A-6020 Innsbruck, Austria
[2] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA
[3] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA
[4] Hokkaido Univ, Sch Med, Dept Surg 1, Sapporo, Hokkaido 060, Japan
关键词
bilirubin; biliverdin; atherosclerosis; heme oxygenase; cell cycle; smooth muscle; retinoblastoma; MAPK;
D O I
10.4161/cc.6.1.3700
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have recently shown that the natural bile pigment bilirubin has antiproliferative effects on vascular smooth muscle cells (VSMCs). Bilirubin is the end product of heme catabolism mediated by heme oxygenases and has for decades been considered a toxic waste product of our bodies. However, 14 separate studies and a meta-analysis have documented an inverse correlation between atherosclerosis and the levels of bilirubin in normal individuals. Having high normal or supranormal levels of bilirubin is associated with less atherosclerotic-type disease as compared with that in individuals with low normal levels of bilirubin. This combined with experimental data showing anti-atherosclerotic properties of the enzyme heme oxygenase-1 encouraged us to hypothesize that bilirubin and its precursor biliverdin, would act to ameliorate components of atherosclerosis, in a manner similar to what has been shown with HO-1. Both did so in an animal model of restenosis in which vascular smooth muscle cell proliferation leads to intimal proliferation and causes narrowing of the vessels. We also analyzed the antiproliferative effects of the bile pigments in an in vitro system where bilirubin/biliverdin caused p53 dependent cell cycle arrest by hypophosphorylation of the retinoblastoma tumor suppressor protein in growth factor stimulated VSMCs.
引用
收藏
页码:39 / 43
页数:5
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