Pro-angiogenesis action of thyroid hormone and analogs in a three-dimensional in vitro microvascular endothelial sprouting model.
OBJECTIVE
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.
Mousa
S A
SA
The Pharmaceutical Research Institute, Albany College of Pharmacy, Albany, NY, USA. mousas@acp.edu
Davis
F B
FB
Mohamed
S
S
Davis
P J
PJ
Feng
X
X
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D013974:Thyroxine / Q000031:analogs & derivatives* / Q000502:physiology*; D014284:Triiodothyronine / Q000502:physiology*
D014284:Triiodothyronine; C011126:tetraiodothyroacetic acid; D013974:Thyroxine