Knockdown of caveolin-1 by antisense oligonucleotides impairs angiogenesis in vitro and in vivo

Biochem Biophys Res Commun. 2000 Sep 24;276(2):756-61. doi: 10.1006/bbrc.2000.3484.


Knock-out of the gene coding for caveolin-1, the main organizer of caveolae, has not yet been performed. We devised a strategy to knock-down caveolin-1 gene expression using antisense oligodeoxynucleotides (ODNs). Seven ODNs, covering different regions of caveolin-1 mRNA, were screened by Western blot analysis of caveolin-1 levels. The most active and specific was found to reduce caveolin-1 protein levels by 70% at 1 microM concentration and its action, as demonstrated by a marked reduction (about 50%) in caveolin-1 mRNA levels, was due to a true antisense mechanism. In HUVEC treated with the active ODN, caveolae were undetectable by confocal and electron microscopy, while their number was not affected when cells were treated with a scrambled ODN. Using the fibrin gel 3 D angiogenesis test we established that the active (but not the scrambled) ODN strongly suppressed capillary-like tube formation. Moreover, an antisense tailored against chicken caveolin-1 mRNA, when tested using the chorio-allantoic membrane technique, dramatically reduced vessel formation at doses (10-20 microg) under which control ODNs were ineffective and devoid of toxicity. Thus, it is likely that caveolin-1 down regulation, followed by caveolae disruption, impairs angiogenesis in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Caveolin 1
  • Caveolins / antagonists & inhibitors*
  • Caveolins / genetics
  • Caveolins / physiology
  • Cells, Cultured
  • Chick Embryo
  • Endothelial Growth Factors / genetics
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Gene Expression Regulation
  • Humans
  • Lymphokines / genetics
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Angiogenesis Inhibitors
  • CAV1 protein, human
  • Caveolin 1
  • Caveolins
  • Endothelial Growth Factors
  • Lymphokines
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors