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

Shaker A. Mousa, Laura J. O'Connor, Joel J. Bergh, Faith B. Davis, Thomas (Tom) Scanlan, Paul J. Davis

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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 TRβ and TRα. In contrast, the hormone analogue GC-1 also stimulates transcriptional activation via TRβ1. 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 αvβ3 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 αvβ3 integrin receptor, and are dependent on MAPK activation.

Original languageEnglish (US)
Pages (from-to)356-360
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume46
Issue number3
DOIs
StatePublished - Sep 2005
Externally publishedYes

Fingerprint

Thyroid Hormones
Integrins
Sepharose
Fibroblast Growth Factor 2
Chorioallantoic Membrane
Cell Membrane
Mitogen-Activated Protein Kinases
Thyroxine
Transcriptional Activation
Thyronines
Thyroid Hormone Receptors
GC 1 compound
Triiodothyronine
Protein Kinase Inhibitors
Cytoplasmic and Nuclear Receptors
Endothelial Cells
Hormones

Keywords

  • αvβ3 integrin
  • Angiogenesis
  • Fibroblast growth factor 2
  • Mitogen-activated protein kinase
  • Thyroid hormone analogues

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

The proangiogenic action of thyroid hormone analogue GC-1 is initiated at an integrin. / Mousa, Shaker A.; O'Connor, Laura J.; Bergh, Joel J.; Davis, Faith B.; Scanlan, Thomas (Tom); Davis, Paul J.

In: Journal of Cardiovascular Pharmacology, Vol. 46, No. 3, 09.2005, p. 356-360.

Research output: Contribution to journalArticle

Mousa, Shaker A. ; O'Connor, Laura J. ; Bergh, Joel J. ; Davis, Faith B. ; Scanlan, Thomas (Tom) ; Davis, Paul J. / The proangiogenic action of thyroid hormone analogue GC-1 is initiated at an integrin. In: Journal of Cardiovascular Pharmacology. 2005 ; Vol. 46, No. 3. pp. 356-360.
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