Thyrotropin Stimulates Production of Procoagulant and Vasodilatative Factors in Human Aortic Endothelial Cells

Abstract

Thyroid diseases have been associated with pathophysiological changes in the vasculature that may result from altered thyroid hormone production or to direct effect of elevated thyrotropin (TSH) levels on smooth muscle cells. A direct effect of TSH on vascular endothelium has not been considered. In the present study a strain of human aortic endothelial cells has been stimulated with TSH, and vascular parameters correlated with the atherosclerotic process have been analyzed. Addition of TSH induced an increase of cyclic AMP (cAMP) concentration in human aortic endothelial cells. Furthermore it induced a decrease of endothelin (from 30 ± 2.5 to 13 ± 1 fmol/mL) and of tissue plasminogen activator secretion (from 2,800 ± 200 to 1,600 ± 150 ng/mL). On the other hand, it increased nitric oxide (from 148 ± 8 to 211 ± 12 μM). TSH did not affect plasminogen activator inhibitor 1. Similar results were obtained when immunoglobulin Gs (IgGs) from Graves' disease patients were used. In conclusion, our findings suggest that TSH and IgGs from Graves' disease patients could stimulate endothelial cells, increasing the secretion of procoagulant and vasodilatative factors, and that cAMP is involved in the transduction pathway. These findings are consistent with modifications of the fibrinolytic system reported in hypothyroidism and in Graves' disease. On the other hand, the increase of vascular resistance found in patients with hypothyroidism may be due to the altered thyroid hormone production and not to TSH directly, or to a different effect of TSH on peripheral vessels.