GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu.
GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu.
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GSTM1调节尿毒症环境中内皮粘附分子的表达。
DOI：
10.1155/2021/6678924
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发表时间：
2021
影响因子：
--
通讯作者：
Simic T
中科院分区：
文献类型：
--
作者：
Jerotic D;Suvakov S;Matic M;Alqudah A;Grieve DJ;Pljesa-Ercegovac M;Savic-Radojevic A;Damjanovic T;Dimkovic N;McClements L;Simic T
谷胱甘肽 S-转移酶 M1 (GSTM1) 是一种 II 期解毒和抗氧化酶，其缺失多态性会增加 ESRD 患者对终末期肾病 (ESRD) 以及心血管疾病 (CVD) 的易感性，并导致其心血管存活期缩短。迄今为止，尚未研究 GSTM1 下调导致尿毒症条件下内皮细胞氧化应激和炎症的机制。因此，本研究的目的是阐明 GSTM1 敲低对暴露于尿毒症血清的人脐静脉内皮细胞 (HUVEC) 中氧化应激和一组炎症标志物表达的影响。此外，我们的目的是辨别 GSTM1 缺失基因型是否与 ESRD 患者的血清粘附分子水平相关。用尿毒症血清处理的 HUVEC 表现出氧化还原平衡受损，其特征是脂质过氧化增强和抗氧化酶活性降低，与 GSTM1 敲低无关。为了应对尿毒症损伤，HUVEC 表现出一系列炎症细胞因子表达的改变，包括激活调节的视黄醇结合蛋白 4 (RBP4)、正常 T 细胞表达和分泌 (RANTES)、C 反应蛋白 (CRP)、血管生成素、dickkopf-1 (Dkk-1) 和血小板因子 4 (PF4)。 HUVEC 中 GSTM1 敲低显示单核细胞趋化蛋白-1 (MCP-1) 上调，MCP-1 是一种参与调节单核细胞迁移和粘附的细胞因子。这些细胞还表现出细胞内和血管细胞粘附分子（ICAM-1 和 VCAM-1）上调。根据这些发现，与具有 GSTM1 活性基因型的患者相比，缺乏 GSTM1 的 ESRD 患者的血清 ICAM-1 和 VCAM-1（sICAM-1 和 sVCAM-1）水平升高。基于这些结果，可以得出结论，尿毒症血清中内皮细胞的孵育诱导了氧化还原失衡，并伴随着与动脉硬化和动脉粥样硬化有关的一系列细胞因子的表达改变。 GSTM1 下调与粘附分子表达改变的关联可能至少在一定程度上导致 ESRD 患者对 CVD 的易感性增加。
Deletion polymorphism of glutathione S-transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end-stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether GSTM1-null genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol-binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein (CRP), angiogenin, dickkopf-1 (Dkk-1), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). In accordance with these findings, the levels of serum ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) were increased in ESRD patients lacking GSTM1, in comparison with patients with the GSTM1-active genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD.
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影响因子：
4.8
作者：
Ito, Shunsuke;Osaka, Mizuko;Yoshida, Masayuki
通讯作者：
Yoshida, Masayuki
影响因子：
4.8
作者：
Cho, SG;Lee, YH;Choi, EJ
通讯作者：
Choi, EJ
影响因子：
5.7
作者：
Bikfalvi, A
通讯作者：
Bikfalvi, A
DOI：
10.1161/01.atv.0000189159.96900.d9
发表时间：
2005-12-01
影响因子：
8.7
作者：
Dickhout, JG;Hossain, GS;Austin, RC
通讯作者：
Austin, RC
影响因子：
5.3
作者：
Bobbert, Thomas;Raila, Jens;Spranger, Joachim
通讯作者：
Spranger, Joachim