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International Angiology 2006 December;25(4):407-13


language: English

Pro-angiogenesis action of thyroid hormone and analogs in a three-dimensional in vitro microvascular endothelial sprouting model

Mousa S. A. 1, Davis F. B. 2, Mohamed S. 1, Davis P. J. 2, 3, 4, Feng X. 1

1 The Pharmaceutical Research Institute, Albany College of Pharmacy, Albany, NY, USA 2 Department of Veterans Affairs Medical Center Ordway Research Institute, Inc., Albany, NY, USA 3 Wadsworth Center of the New York State Department of Health, Albany, NY, USA 4 Albany Medical College, Albany, NY, USA


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 10-7-10-9 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 αvβ3 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 αvβ3 integrin receptors, and is MAPK-dependent.

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