Proangiogenic action of thyroid hormone is fibroblast growth factor-dependent and is initiated at the cell surface
Proangiogenic action of thyroid hormone is fibroblast growth factor-dependent and is initiated at the cell surface
复制标题
DOI：
10.1161/01.res.0000130784.90237.4a
复制
发表时间：
2004-06-11
影响因子：
20.1
通讯作者：
Davis, PJ
中科院分区：
文献类型：
--
作者：
Davis, FB;Mousa, SA;Davis, PJ
The effects of thyroid hormone analogues on modulation of angiogenesis have been studied in the chick chorioallantoic membrane model. Generation of new blood vessels from existing vessels was increased 3-fold by either L-thyroxine (T-4; 10(-7) mol/L) or 3,5,3'-triiodo-L-thyronine (10(-9) mol/L). T-4-agarose reproduced the effects of T-4, and tetraiodothyroacetic acid (tetrac) inhibited the effects of both T-4 and T-4-agarose. Tetrac itself was inactive and is known to block actions of T-4 on signal transduction that are initiated at the plasma membrane. T-4 and basic fibroblast growth factor (FGF2) were comparably effective as inducers of angiogenesis. Low concentrations of FGF2 combined with submaximal concentrations of T-4 produced an additive angiogenic response. Anti-FGF2 inhibited the angiogenic effect of T-4. The proangiogenic effects of T-4 and FGF2 were blocked by PD 98059, a mitogen-activated protein kinase ( MAPK) pathway inhibitor. Endothelial cells (ECV304) treated with T-4 or FGF2 for 15 minutes demonstrated activation of MAPK, an effect inhibited by PD 98059 and the protein kinase C inhibitor CGP41251. Reverse transcription-polymerase chain reaction of RNA extracted from endothelial cells treated with T-4 revealed increased abundance of FGF2 transcript at 6 to 48 hours, and after 72 hours, the medium of treated cells showed increased FGF2 content, an effect inhibited by PD 98059. Thus, thyroid hormone is shown to be a proangiogenic factor. This action, initiated at the plasma membrane, is MAPK dependent and mediated by FGF2.
