Milani Attabak Toofani, Khadem-Ansari Mohammad Hassan, Rasmi Yousef
Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, I.R. Iran.
Res Pharm Sci. 2018 Dec;13(6):546-556. doi: 10.4103/1735-5362.245966.
Atherosclerosis is a multifactorial disorder, which affects the arterial wall. It has been reported that, hypothyroidism and thyroid hormone deficiency are related to cardiovascular disorders. Also, endothelial dysfunction plays an essential role in the development of atherosclerosis. We aimed to evaluate the effects of thyroid-stimulating hormone (TSH) on pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), angiogenic vascular endothelial growth factor (VEGF) and leukocyte adhesion, intercellular adhesion molecule 1 (ICAM-1) and E-selectin in human umbilical vein endothelial cells (HUVECs). In this study, HUVEC cells were treated with 1 and 2 μM of TSH in different treatment times. The gene and protein expression of ICAM-1, VEGF, and E-selectin were performed by real-time polymerase chain reaction and western blotting, respectively. Likewise, TNF-α and IL-6 protein levels were determined by the ELISA method. VEGF, ICAM-1, and E-selectin as endothelial dysfunction markers and also, TNF-α and IL-6 as pro-inflammatory cytokines were detectable in HUVEC. Besides, the results of this study revealed that TSH treatment down-regulates TNF-α and IL-6. Evaluating the gene and protein expression data revealed the upregulation of ICAM-1, E-selectin, and VEGF in TSH treated cases in different periods of exposure. Considering the multiple actions of TSH, it could be concluded that TSH plays a controversial role in atherogenesis by anti-inflammatory effects and on the other side, angiogenesis and leukocyte adhesion induction which is related to vascular cell proliferation.
动脉粥样硬化是一种影响动脉壁的多因素疾病。据报道，甲状腺功能减退和甲状腺激素缺乏与心血管疾病有关。此外，内皮功能障碍在动脉粥样硬化的发展中起着至关重要的作用。我们旨在评估促甲状腺激素（TSH）对人脐静脉内皮细胞（HUVECs）中促炎肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、血管生成血管内皮生长因子（VEGF）以及白细胞黏附、细胞间黏附分子1（ICAM-1）和E-选择素的影响。在本研究中，HUVEC细胞在不同处理时间用1μM和2μM的TSH进行处理。ICAM-1、VEGF和E-选择素的基因和蛋白表达分别通过实时聚合酶链反应和蛋白质印迹法进行检测。同样，TNF-α和IL-6蛋白水平通过酶联免疫吸附测定法测定。VEGF、ICAM-1和E-选择素作为内皮功能障碍标志物，以及TNF-α和IL-6作为促炎细胞因子在HUVEC中均可检测到。此外，本研究结果显示TSH处理可下调TNF-α和IL-6。评估基因和蛋白表达数据发现，在不同暴露时间段接受TSH处理的病例中，ICAM-1、E-选择素和VEGF上调。考虑到TSH的多种作用，可以得出结论，TSH在动脉粥样硬化形成中通过抗炎作用发挥了有争议的作用，另一方面，它诱导血管生成和白细胞黏附，这与血管细胞增殖有关。
