title: Effect of Thyrotropin on Osteopontin, Integrin αvβ3,and VCAM-1 in the Endothelium via Activation of Akt.
abstract: Numerous epidemiological studies have shown that subclinical hypothyroidism (SCH) can impair endothelial function and cause dyslipidemia. Studies have evaluated the effects of thyroid stimulating hormone (TSH) on endothelial cells, but the mechanism underlying the proatherosclerotic effect of increased TSH levels remains unclear. In the present study, SCH rat models were established in thyroidectomized Wistar rats that were given ʟ-T₄ daily. The results showed that in vivo, the expression of osteopontin (OPN) vascular cell adhesion molecule (VCAM-1), and levels of integrin αvβ₃ in the aortic tissue in SCH and Hypothyroidism (CH) groups was higher than in the control group. However, the effect in the SCH group was higher than in the CH group. In vitro, results showed that different concentration and time gradients of TSH stimulation could increase the expression of OPN, VCAM-1, and integrin αvβ₃, and this was accompanied by extracellular signal regulated kinase 1/2 (Erk1/2) and Akt activation in human umbilical vein endothelial cells (HUVECs). TSH induced elevation of these proatherosclerotic factors was partially suppressed by a specific Akt inhibitor but not by a specific Erk inhibitor. Findings suggested that the endothelial dysfunction caused by SCH was related to increased proatherosclerotic factors induced by TSH via Akt activation.
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. cherylyanyumeng@hotmail.com.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. winnterrain0923@tom.com.
authors.forename: Fengwei
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. laiyaxin811005@126.com.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. why_endocrinology@foxmail.com.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. liuaihuacmu@163.com.
authors.forename: Aihua
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. chuyuan0215@163.com.
authors.forename: Chuyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. yuan-anpo@126.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. twp@vip.163.com.
authors.forename: Weiping
authors.initials: W
authors.lastname: Teng
authors.affiliation: Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China. shanzhongyan@medmail.com.cn.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Shan
keywords: atherosclerosis; osteopontin; subclinical hypothyroidism; thyrotropin