The proangiogenic action of thyroid hormone analogue GC-1 is initiated at an integrin

J Cardiovasc Pharmacol. 2005 Sep;46(3):356-60. doi: 10.1097/01.fjc.0000175438.94906.a0.


Our early reported investigations have demonstrated potent proangiogenic effects of L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3) in the chick chorioallantoic membrane (CAM) model. Tetraiodothyroacetic acid (tetrac) blocks T4 binding to plasma membranes and its pro-angiogenic effect. T4/T3 stimulates expression of fibroblast growth factor 2 (FGF2) in endothelial cells. Thyroid hormone (T4/T3) is principally responsible for transcriptional activation mediated by nuclear thyroid hormone receptors TRbeta and TRalpha. In contrast, the hormone analogue GC-1 also stimulates transcriptional activation via TRbeta1. In the present study, we have defined the effect of GC-1, compared with T4 and T4-agarose, on angiogenesis in the CAM assay. GC-1 demonstrated a proangiogenic effect similar to that of T4 and T4-agarose. Tetrac inhibited GC-1- and T4-induced angiogenesis, indicating dependence on T4 and GC-1 binding to plasma membranes. The effects of GC-1, T4-agarose, and FGF2 were blocked by PD 98059, a mitogen-activated protein kinase (MAPK) pathway inhibitor. Additionally, the alphavbeta3 integrin antagonist XT199 inhibited angiogenesis induced by T4-agarose, GC-1, or FGF2. Thus, the proangiogenic effects of GC-1 and T4 are initiated at the plasma membrane, require interaction with alphavbeta3 integrin receptor, and are dependent on MAPK activation.

Publication types

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

MeSH terms

  • Acetates / pharmacology*
  • Animals
  • Cell Membrane / drug effects
  • Chick Embryo
  • Chorion / blood supply
  • Chorion / drug effects
  • Fibroblast Growth Factor 2 / physiology
  • Indicators and Reagents
  • Integrin alphaVbeta3 / antagonists & inhibitors
  • Integrin alphaVbeta3 / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Phenols / pharmacology*
  • Regional Blood Flow / drug effects
  • Thyroid Hormone Receptors beta / drug effects
  • Thyroxine / analogs & derivatives
  • Thyroxine / pharmacology


  • Acetates
  • GC 1 compound
  • Indicators and Reagents
  • Integrin alphaVbeta3
  • Phenols
  • Thyroid Hormone Receptors beta
  • Fibroblast Growth Factor 2
  • Mitogen-Activated Protein Kinases
  • tetraiodothyroacetic acid
  • Thyroxine