Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease

Nat Med. 1998 Feb;4(2):222-7. doi: 10.1038/nm0298-222.


We postulated that activation of a genetic program that tonically inhibits intimal cell death is a necessary condition for the pathogenesis of vascular disease. Studies of vascular lesions in humans and animal models documented increased expression of the anti-apoptotic gene product Bcl-xL within intimal cells. Downregulation of intimal cell bcl-xL expression with the use of antisense oligonucleotides induced apoptosis and acute regression of vascular lesions. These findings indicate that apoptosis regulatory genes such as bcl-xL are critical determinants of intimal lesion formation and that targeted apoptosis may be a novel therapy for intimal vascular disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Down-Regulation
  • Gene Expression Regulation
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / pathology
  • Oligonucleotides, Antisense / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Rabbits
  • Tunica Intima / drug effects
  • Tunica Intima / pathology*
  • Vascular Diseases / pathology*
  • bcl-X Protein


  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein