Control of angiogenesis with synthetic heparin substitutes

Science. 1989 Mar 17;243(4897):1490-3. doi: 10.1126/science.2467380.

Abstract

Many diseases are dominated by persistent growth of capillary blood vessels. Tumor growth is also angiogenesis-dependent. Safe and effective angiogenesis inhibitors are needed to determine whether control of angiogenesis would be therapeutic. Heparin and certain steroids, administered together, can inhibit angiogenesis in a synergistic manner. This "pair" effect suggested that specific hydrophilic cycloamyloses may be suitable heparin substitutes. beta-Cyclodextrin tetradecasulfate administered with a steroid inhibits angiogenesis at 100 to 1000 times the effectiveness of heparin in the chick embryo bioassay. This cyclic oligosaccharide also augments the anti-angiogenic effect of angiostatic steroids against corneal neovascularization in rabbits when beta-cyclodextrin tetradecasulfate and a steroid are inserted into the cornea or applied topically as eyedrops.

Publication types

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

MeSH terms

  • Animals
  • Cyclodextrins / pharmacology*
  • Dextrins / pharmacology*
  • Heparin / analogs & derivatives*
  • Heparin / pharmacology
  • Heparitin Sulfate / analogs & derivatives
  • Heparitin Sulfate / pharmacology
  • Neovascularization, Pathologic*
  • Rabbits
  • Starch / pharmacology*
  • Steroids / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cyclodextrins
  • Dextrins
  • Steroids
  • Starch
  • Heparin
  • Heparitin Sulfate