Department of Nephrology, Kuang-Tien General Hospital, Taichung, 433, Taiwan, Republic of China.
Institute of Biomedical Nutrition, Hung-Kuang University, Taichung, 433, Taiwan, Republic of China.
Biol Trace Elem Res. 2020 Jan;193(1):14-22. doi: 10.1007/s12011-019-01685-8. Epub 2019 Mar 7.
Patients undergoing long-term hemodialysis (HD) are known to have abnormal blood concentrations of antioxidant minerals; concurrent oxidative stress can contribute to increased vascular calcification. This study aims to evaluate the associations between circulating antioxidant minerals and clinical biomarkers of vascular calcification in HD patients. Blood biochemical parameters, antioxidant minerals (selenium (Se), zinc (Zn), copper (Cu), and magnesium (Mg)), and several promoters and inhibitors of calcification (matrix Gla protein (MGP), fibroblast growth factor-23 (FGF-23), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitors of metalloproteinase (TIMP-1 and -2)) were determined in HD patients (n = 62) and age- and sex-matched healthy individuals (n = 30). Compared with healthy subjects, HD patients had significantly lower plasma concentrations of Se and Zn, increased Cu and Mg, and higher levels of oxidative stress and inflammatory markers (Cu/Zn ratios, malondialdehyde (MDA), advanced glycation end products (AGEs), and C-reactive protein (CRP)). We observed that HD patients had significantly lower concentrations of MGP and higher levels of FGF-23, MMP-2 and -9, TIMP-1 and -2, and MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios. We also observed significant relationships between the concentrations of these minerals and calcification biomarkers in HD patients. These results suggest that changes in the homeostasis of antioxidant minerals (Se, Zn, Cu, and Mg) may contribute to the effects of oxidative stress and inflammatory status, thereby participating in the mechanism for accelerated vascular calcification in patients undergoing long-term HD.
长期接受血液透析 (HD) 的患者已知其抗氧化矿物质的血液浓度异常;同时存在的氧化应激可能导致血管钙化增加。本研究旨在评估 HD 患者循环抗氧化矿物质与血管钙化的临床生物标志物之间的相关性。在 HD 患者(n=62)和年龄及性别匹配的健康个体(n=30)中测定了血液生化参数、抗氧化矿物质(硒(Se)、锌(Zn)、铜(Cu)和镁(Mg))以及几种钙化促进剂和抑制剂(基质 Gla 蛋白(MGP)、成纤维细胞生长因子-23(FGF-23)、基质金属蛋白酶(MMP-2 和 -9)和金属蛋白酶组织抑制剂(TIMP-1 和 -2))。与健康受试者相比,HD 患者的血浆 Se 和 Zn 浓度明显降低,Cu 和 Mg 浓度升高,氧化应激和炎症标志物(Cu/Zn 比值、丙二醛(MDA)、晚期糖基化终产物(AGEs)和 C 反应蛋白(CRP))水平升高。我们观察到 HD 患者的 MGP 浓度明显降低,而 FGF-23、MMP-2 和 -9、TIMP-1 和 -2 以及 MMP-2/TIMP-2 和 MMP-9/TIMP-1 比值升高。我们还观察到这些矿物质的浓度与 HD 患者钙化生物标志物之间存在显著关系。这些结果表明,抗氧化矿物质(Se、Zn、Cu 和 Mg)的体内平衡变化可能有助于氧化应激和炎症状态的影响,从而参与长期接受 HD 的患者加速血管钙化的机制。