Impaired release of tissue plasminogen activator from the endothelium in Graves' disease - indicator of endothelial dysfunction and reduced fibrinolytic capacity.
BACKGROUND
Patients with hyperthyroidism have increased plasma levels of von Willebrand factor (vWF). Changes in tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1), another two endothelium-derived proteins and modulators of blood fibrinolytic activity, have not been reported in hyperthyroidism.


METHODS
The release of t-PA by vascular endothelial cells after venous occlusion, basal blood concentrations of t-PA, PAI-1 and vWF were studied in 33 patients with hyperthyroidism, with most of them followed up 30 days after iodine radiotherapy.


RESULTS
Compared with control subjects, both the basal t-PA levels in plasma and the increase in t-PA levels with venous occlusion were significantly decreased in patients (P < 0.001), whereas plasma PAI-1 and vWF levels were increased greatly (P < 0.001). At follow-up, patients with normal plasma free thyroxine (T4) and total tri-iodothyronine (T3) showed similar plasma levels of t-PA, PAI-1, vWF and release of t-PA from endothelial cells as the control subjects (P > 0.05). In those with persistent elevated T4 or T3 levels, however, the basal plasma t-PA level and the released t-PA from endothelial cells during venous occlusion were significantly lower than in the control subjects (P < 0.001 and P < 0.005), and blood concentrations of PAI-1 and vWF did not return to the normal range (P < 0.001 and P < 0.001). In all patients, serum thyroid hormone concentrations were inversely correlated with basal plasma t-PA (T4: r = -0.549, P < 0. 001; T3: r = -0.463, P < 0.001) and released t-PA by endothelial cells (T4: r = -0.505, P < 0.001; T3: r = -0.450, P < 0.001) but strongly correlated with plasma PAI-1 (T4: r = 0.613, P < 0.001; T3: r = 0.577, P < 0.001) and vWF (T4: r = 0.457, P < 0.001; T3: r = 0. 564, P < 0.001).


CONCLUSIONS
Hyperthyroid patients may experience vascular endothelial dysfunction and reduced fibrinolytic activity in blood.
Li
Y
Y
Affiliated Hospital of Zunyi Medical School, Zunyi 563003, China. YOU.LI@ummed.edu
Chen
H
H
Tan
J
J
Wang
X
X
Liang
H
H
Sun
X
X
D000328:Adult; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator