Effects of TSH on the function of human umbilical vein endothelial cells.
Recent studies have reported that subclinical hypothyroidism (SCH) is associated with atherosclerosis (AS). Thyroid hormone is maintained at normal levels in patients with SCH, whereas TSH is increased. However, the pathogenesis of AS in association with SCH is only partially understood. In addition, endothelial dysfunction plays an important role in the development of AS. The purpose of the present research was to study the direct effect of TSH on human umbilical vein endothelial cells (HUVECs). The expression of some genes associated with endothelial dysfunction after treatment with TSH was evaluated by real-time PCR and western blotting respectively. At first, we showed that the TSH receptor (TSHR) is expressed in HUVECs. We also provide evidence indicating that TSH treatment promotes tumor necrosis factor α-induced endothelial cells interactions by upregulating the expression of the adhesion molecules intercellular adhesion molecule-1. Furthermore, the expression of endothelial nitric oxide synthase (eNOS) and prostacyclin (PGI₂) was significantly attenuated following treatment with TSH in dose- and time-dependent manner. Conversely, the results indicated that TSH upregulated endothelin-1 (ET1) mRNA and protein expression in HUVECs, similar effects were observed for plasminogen activator inhibitor-1 (PAI1) after treatment with various concentrations of TSH. Taken together, these results demonstrate that elevated TSH can promote endothelial dysfunction by altering gene expression in HUVECs.
Departments of Endocrinology General Surgery Ultrasonography, Gansu Provincial Hospital, 204 Dong Gang West Road, Lanzhou 730000, China.
Limin
L
Tian
Luyan
L
Zhang
Jing
J
Liu
Tiankang
T
Guo
Cuixia
C
Gao
Jing
J
Ni
D000818:Animals; D002417:Cattle; D015536:Down-Regulation / Q000187:drug effects; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D011464:Epoprostenol / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D019332:Endothelin-1; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D013972:Thyrotropin; D011464:Epoprostenol; D052250:Nitric Oxide Synthase Type III
atherosclerosis; human umbilical vein endothelial cells; subclinical hypothyroidism; thyroid-stimulating hormone