Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, New York 12144, USA.
Clin Appl Thromb Hemost. 2010 Jun;16(3):288-93. doi: 10.1177/1076029609348315. Epub 2009 Nov 10.
The endogenous thyroid hormones L-thyroxine (T(4)) and 3,5,3'-triiodo-L-thyronine (T(3)) induce angiogenesis via an endothelial cell iodothyronine receptor on integrin alphaVbeta3. This receptor also exists on platelets. Diiodothyropropionic acid (DITPA) and GC-1, a noniodinated thyroid hormone analog, also induce angiogenesis. Here we examined the effects of iodothyronines (L-T(4) vs L-T(3)) and analogs DITPA and GC-1 on human platelet function. Subthreshold aggregation of platelets obtained from healthy human donors was induced with collagen. Platelet activation (proaggregation) and adenosine triphosphate (ATP) secretion (degranulation) induced by L-T( 4), L-T(4)-agarose, L-T(3), DITPA, or GC-1 were determined simultaneously. Platelet aggregation and ATP secretion induced by a subthreshold level of collagen were enhanced 3-fold by either L-T(4) or L-T( 4)-agarose (0.01 micromol/L) as compared to control, whereas, L-T( 3), DITPA, or GC-1 had no effect under the same conditions. The platelet proaggregatory and degranulation effects of L-T(4) were blocked by the alphavbeta3 antagonist XT199 (0.1 micromol/ L) and by tetraiodothyroacetic acid (tetrac; 0.1 micromol/L). Tetrac inhibits binding of thyroid hormone analogs to the receptor on alphavbeta3 and lacks thyromimetic activity at this site; thus, the proaggregatory action of L-T(4) likely involves the cell surface receptor on integrin alphavbeta3. The thyroid hormone receptor (TR) on human platelets but not endothelial cells distinguishes among iodothyronines, reflecting quantitative differences in integrin sites on endothelial cells and platelets or qualitative differences in the phospholipids/protein microenvironment of endothelial and platelet membranes that can affect integrin function. Additional studies in different populations with larger sample sizes are warranted to determine the impact of the current findings on clinical interventions.
内源性甲状腺激素 L-甲状腺素（T（4））和 3,5,3'-三碘-L-甲状腺素（T（3））通过整合素 αVβ3 上的内皮细胞碘甲状腺素受体诱导血管生成。该受体也存在于血小板上。二碘甲状腺原氨酸（DITPA）和 GC-1，一种非碘甲状腺激素类似物，也可诱导血管生成。在这里，我们研究了碘甲状腺素（L-T（4）与 L-T（3））和类似物 DITPA 和 GC-1 对人血小板功能的影响。用胶原诱导来自健康人类供体的血小板亚阈值聚集。同时测定 L-T（4）、L-T（4）-琼脂糖、L-T（3）、DITPA 或 GC-1 诱导的血小板活化（促聚集）和三磷酸腺苷（ATP）分泌（脱颗粒）。与对照相比，L-T（4）或 L-T（4）-琼脂糖（0.01µmol/L）诱导的亚阈值水平的胶原诱导的血小板聚集和 ATP 分泌增强了 3 倍，而在相同条件下，L-T（3）、DITPA 或 GC-1 则没有作用。L-T（4）的血小板促聚集和脱颗粒作用被 alphavbeta3 拮抗剂 XT199（0.1µmol/L）和四碘甲状腺乙酸（tetrac；0.1µmol/L）阻断。Tetrac 抑制甲状腺激素类似物与 alphavbeta3 上的受体结合，并且在该部位缺乏甲状腺素活性；因此，L-T（4）的促聚集作用可能涉及整合素 alphavbeta3 上的细胞表面受体。人血小板上的甲状腺激素受体（TR）而不是内皮细胞可以区分碘甲状腺素，反映了内皮细胞和血小板上整合素位点的定量差异，或者内皮和血小板膜中磷脂/蛋白微环境的定性差异，这些差异会影响整合素的功能。需要在具有更大样本量的不同人群中进行更多研究，以确定当前发现对临床干预的影响。
