Thyroid hormone, hormone analogs, and angiogenesis

Paul J. Davis, Thangirala Sudha, Hung Yun Lin, Shaker A. Mousa

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


Modulation by thyroid hormone and hormone analogs of angiogenesis in the heart after experimental infarction, and in other organs, has been appreciated for decades. Description of a plasma membrane receptor for thyroid hormone on the extracellular domain of integrin αvβ3 on endothelial cells has revealed the complexity of the nongenomic regulation of angiogenesis by the hormone. From αvβ3, the hormone directs transcription of specific vascular growth factor genes, regulates growth factor receptor/growth factor interactions and stimulates endothelial cell migration to a vitronectin cue; these actions are implicated experimentally in tumor-relevant angiogenesis and angioproliferative pulmonary hypertension. Derived from L-thyroxine (T4), tetraiodothyroacetic acid (tetrac) can be covalently bound to a polymer and as Nanotetrac acts exclusively at the hormone receptor on αvβ3 to block actions of T4 and 3,5,3'-triiodo-L-thyronine (T3) on angiogenesis. Other antiangiogenic actions of Nanotetrac include disruption of crosstalk between integrin αvβ3 and adjacent cell surface vascular growth factor receptors, resulting in disordered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF; FGF2) actions at their respective plasma membrane receptors. From αvβ3, Nanotetrac also downregulates expression of VEGFA and epidermal growth factor receptor (EGFR) genes, upregulates transcription of the angiogenesis suppressor gene, thrombospondin 1 (THBS1; TSP1) and decreases cellular abundance of Ang-2 protein and matrix metalloproteinase-9. Existence of this receptor provides new insights into the multiple mechanisms by which thyroid hormone and hormone analogs may regulate angiogenesis at the molecular level. The receptor also offers pharmacological opportunities for interruption of pathological angiogenesis via integrin αvβ3.

Original languageEnglish
Pages (from-to)353-362
Number of pages10
JournalComprehensive Physiology
Issue number1
Publication statusPublished - Jan 1 2016

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology


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