Author(s): Mousa SA, Davis FB, Mohamed S, Davis PJ, Feng X
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Abstract AIM: Our laboratory has recently demonstrated the pro-angiogenesis effects of thyroid hormone in the chick chorioallantoic membrane model. METHODS: Generation of new blood vessels from existing vessels was promoted two- to three-fold by either L-thyroxine (T4) or 3,5,3'-triiodo-L-thyronine (T3) at total hormone concentrations of T7-T9 M. RESULTS: T4-agarose, a formulation of thyroid hormone that does not cross the cell membrane, produced a potent pro-angiogenesis effect comparable to that obtained with T3 or T4. In the present investigation, T3, T4, T4-agarose, and basic fibroblast growth factor, each added to vascular endothelial growth factor, produced comparable pro-angiogenesis effects in the in vitro three-dimensional human microvascular endothelial sprouting model. The pro-angiogenesis effect of the thyroid hormone analogs was blocked by PD 98059, an inhibitor of the mitogen-activated protein kinase (MAPK; ERK1/2) signal transduction cascade. A specific avb3 integrin antagonist (XT199) also inhibited the pro-angiogenesis effect of either thyroid hormone analogs or T4-agarose. Tetrac, a thyroid hormone analog that blocks cell surface-initiated actions of T4 and T3, inhibited the pro-angiogenesis response of thyroid hormone. CONCLUSIONS: T4, T3, and T4-agarose are pro-angiogenic in the three-dimensional human microvascular endothelial sprouting model, an action that is initiated at the plasma membrane, involves avb3 integrin receptors, and is MAPK-dependent.
This article was published in Int Angiol
and referenced in Journal of Cancer Science & Therapy