Selenium modulates MMP2 expression through the TGFβ1/Smad signalling pathway in human umbilical vein endothelial cells and rabbits following lipid disturbance
Selenium modulates MMP2 expression through the TGFβ1/Smad signalling pathway in human umbilical vein endothelial cells and rabbits following lipid disturbance
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硒通过 TGF beta 1/Smad 信号通路调节脂质紊乱后人脐静脉内皮细胞和兔中 MMP2 的表达
DOI：
10.1016/j.jtemb.2017.04.006
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发表时间：
2017-01-01
影响因子：
3.5
通讯作者：
Gao, Xiuren
中科院分区：
文献类型：
--
作者：
Xu, Chenggui;Lu, Guihua;Gao, Xiuren
背景：高脂肪饮食是冠心病的主要危险因素。基质金属蛋白酶（MMP）在许多心血管疾病中表达改变。硒是动物体内重要的微量元素，与心血管疾病有着密切的关系。TGF β 1/Smad信号通路普遍存在于多种组织细胞中，也与心血管疾病的发生发展有关。因此，在本研究中，我们旨在确定硒对脂质代谢、动脉粥样硬化斑块形成和MMP2表达的影响及其潜在的作用机制。方法与结果：体内试验：雄性新西兰大白兔24只，随机分为4组：常规饲粮组、高脂饲粮组、高脂饲粮+硒组和常规饲粮+硒组。高脂饲料在第12周引起家兔脂质紊乱。添加硒降低了总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和甘油三酯（TG）水平（p < 0.01）。补充硒还能抑制胸主动脉中MMP2的过表达。体外实验：用不同浓度的硒或ox-LDL处理人脐静脉内皮细胞（HUVECs）。Ox-LDL通过增加TGF β 1、pSmad2、pSmad3、Smad3的表达促进MMP2的表达（p < 0.01）。硒通过调节TGF β 1/Smad信号通路减弱MMP2过表达。结论：硒通过改善体内脂质代谢抑制高脂饮食诱导的MMP2过表达。在体外，硒通过TGF β 1/Smad信号通路减弱MMP2的过表达。
Background: A high-fat diet is a major risk factor for coronary heart diseases. Matrix metalloprotease (MMP) expression is changed in many cardiovascular diseases. Selenium, which is an important trace element in animals, has a close relationship with cardiovascular diseases. The TGF beta 1/Smad signalling pathway is ubiquitous in diverse tissues and cells, and it is also associated with the occurrence and development of cardiovascular diseases. Therefore, in this study, we aimed to determine selenium's effect on lipid metabolism, atherosclerotic plaque formation, and MMP2 expression, as well as the underlying functional mechanism.Methods and results: In vivo tests: 24 male New Zealand white rabbits were randomly divided into 4 groups: regular diet, high-fat diet, high-fat diet + selenium and regular diet + selenium groups. The high-fat diet induced the lipid disturbances of rabbits at week 12. Selenium supplementation lowered total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels (p < 0.01). Selenium supplementation also suppressed MMP2 over-expression in thoracic aortas. In vitro tests: Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of selenium or ox-LDL. Ox-LDL promoted MMP2 expression by increasing TGF beta 1, pSmad2, pSmad3 and Smad3 expression (p < 0.01). Selenium attenuated MMP2 over expression by regulating the TGF beta 1/Smad signalling pathway.Conclusions: Selenium suppressed high-fat diet-induced MMP2 over-expression in vivo by improving lipid metabolism. In vitro, selenium attenuated MMP2 over-expression through the TGF beta 1/Smad signalling pathway.