A natural inhibitor of vascular smooth muscle cell proliferation Academic Article Article uri icon


MeSH Major

  • Electronic Health Records
  • Mental Recall
  • Patient Compliance
  • Patient Education as Topic
  • Patient Satisfaction
  • Primary Health Care


  • Background - Bilirubin, a natural product of heme catabolism by heme oxygenases, was considered a toxic waste product until 1987, when its antioxidant potential was recognized. On the basis of observations that oxidative stress is a potent trigger in vascular proliferative responses, that heme oxygenase-1 is antiatherogenic, and that several studies now show that individuals with high-normal or supranormal levels of plasma bilirubin have a lesser incidence of atherosclerosis-related diseases, we hypothesized that bilirubin would have salutary effects on preventing intimal hyperplasia after balloon injury. Methods and Results - We found less balloon injury-induced neointima formation in hyperbilirubinemic Gunn rats and in wild-type rats treated with biliverdin, the precursor of bilirubin, than in controls. In vitro, bilirubin and biliverdin inhibited serum-driven smooth muscle cell cycle progression at the G1 phase via inhibition of the mitogen-activated protein kinase signal transduction pathways and inhibition of phosphorylation of the retinoblastoma tumor suppressor protein. Conclusions - Bilirubin and biliverdin might be potential therapeutics in vascular proliferative disorders. © 2005 American Heart Association, Inc.

publication date

  • August 16, 2005



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1161/CIRCULATIONAHA.104.528802

PubMed ID

  • 16087796

Additional Document Info

start page

  • 1030

end page

  • 1039


  • 112


  • 7