Sm. Baumgartnerparzer et al., INCREASE BY TRIIODOTHYRONINE OF ENDOTHELIN-1, FIBRONECTIN AND VON-WILLEBRAND-FACTOR IN CULTURED ENDOTHELIAL-CELLS, Journal of Endocrinology, 154(2), 1997, pp. 231-239
Hyperthyroidism is associated with elevated plasma levels of endotheli
um-derived proteins such as von Willebrand factor (vWF), fibronectin (
FN) and endothelin-1 (ET-1). This study was designed to characterize t
he mechanisms involved in this phenomenon at the cellular level. vWF,
FN and ET-1 secretion and mRNA expression were measured in human umbil
ical vein endothelial cells (HUVECs) exposed to tri-iodothyronine (T-3
) for 13 +/- 1 days, using ELISA, Western blot, RIA and Northern blot
analysis respectively. Exposure of HUVECs to T-3 significantly increas
ed vWF secretion (50 ng T-3/ml: 117 +/- 5%, P<0.01; 100 ng T-3/ml: 127
+/- 26%, P<0.01) as well as vWF mRNA expression (50 ng/ml: 116 +/- 13
%, P<0.001; 100 ng/ml: 136 +/- 30%, P<0.002) (results are means +/- S.
D. analysed by the Wilcoxon signed rank test). FN secretion was signif
icantly affected by 50 (145 +/- 42% of control, P<O.05) and 100 (116.8
+/- 16% of control, P<0.05) ng T-3/ml, and FN mRNA expression by 50 n
g T-3/ml (123 +/- 20%, P<O.05). Long-term incubation with T-3 increase
d both ET-1 secretion (25 ng/ml: 124 +/- 25%, P<0.001; 50 ng/ml: 165 /- 53%, P<0.05; 100 ng/ml: 116 +/- 17%, P<0.05) and prepro-ET-1 mRNA e
xpression (25 ng/ml: 112 +/- 16%, P<0.05; 50 ng/ml: 134 +/- 43%, P<0.0
2; 100 ng/ml: 120 +/- 20%, P<0.02). Protein kinase C (PKC) isoforms ep
silon and beta II were not significantly affected by T-3, whereas PKC
alpha was increased in whole cell lysates and in membrane fractions of
cells incubated with 100 but not 50 ng T-3/ml. Prepro-ET-1 mRNA stabi
lity, cell numbers and proliferation, measured by [H-3]thymidine assay
s, remained unaffected in HUVECs after exposure to T-3. These data ind
icate thyroid hormone-induced upregulation of mRNA expression and prot
ein synthesis of vWF, FN and ET-1, by PKC alpha-, beta II- and epsilon
-independent pathways, explaining, at least in part, increased plasma
concentrations of endothelial proteins and peptides in the hyperthyroi
d state.