Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis.
Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis.
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DOI：
10.3892/mmr.2016.5230
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Huiping Zhang;Zhihong Liu;Sheng-chao Ma;Hui Zhang;Fanqi Kong;Yangyang He;Xiaoling Yang;Yanhua Wang;Hua Xu;Anning Yang;Jue Tian;Minghao Zhang;Jun Cao;Yideng Jiang;Xiong Guo
中科院分区：
文献类型：
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作者：
Huiping Zhang;Zhihong Liu;Sheng-chao Ma;Hui Zhang;Fanqi Kong;Yangyang He;Xiaoling Yang;Yanhua Wang;Hua Xu;Anning Yang;Jue Tian;Minghao Zhang;Jun Cao;Yideng Jiang;Xiong Guo
本研究旨在探讨S-腺苷甲硫氨酸（SAM）/S-腺苷同型半胱氨酸（SAH）比值是否是动脉粥样硬化的敏感指标，是否可作为临床诊断动脉粥样硬化的生物标志物。将载脂蛋白E（ApoE）-/-小鼠随机分为四组，并喂食高蛋氨酸饮食15周。采用全自动生化分析仪测定血清同型半胱氨酸（Hcy）水平。使用高效液相色谱法测定SAM和SAH的浓度。采用巢式降落-甲基化特异性-聚合酶链反应分析B1重复元件、脂肪细胞脂肪酸结合蛋白（FABP 4）、单核细胞趋化蛋白-1（MCP-1）和细胞外超氧化物歧化酶（EC-SOD）的甲基化水平。15周后，与正常对照组相比，ApoE-/-对照组、Meth组和Meth-F组的血清Hcy浓度分别显著升高1.15倍、2.54倍和1.17倍（P<0.05）。与正常对照组相比，ApoE-/-对照组、Meth组和Meth-F组的动脉粥样硬化病变的大小分别增加了1.44、2.40和1.45倍（P<0.05）。ApoE-/-对照组、Meth组和Meth-F组SAM浓度分别增加3.02-、3.42-和2.46-倍（P<0.05）。与正常对照组相比，ApoE-/-对照组和Meth组的SAM/SAH比值分别增加了1.67倍和2.75倍。B1重复元件、FABP 4、MCP-1和EC-SOD的甲基化水平降低，表现为低甲基化。这些基因的甲基化状态与血清SAM和SAH水平的比值相关。提示SAM/SAH比值可作为动脉粥样硬化的生物标志物，为临床诊断提供敏感指标。
The present study aimed to confirm whether the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) is a sensitive indicator, and whether it can be used as a biomarker for the clinical diagnosis of atherosclerosis. Apolipoprotein E (ApoE)-/- mice were randomly divided into four groups and fed with a high methionine diet for 15 weeks. Serum levels of homocysteine (Hcy) were measured using an automatic biochemistry analyzer. The concentrations of SAM and SAH were determined using high‑performance liquid chromatography. The methylation levels of B1 repetitive elements, adipocyte fatty acid binding protein (FABP4), monocyte chemoattractant protein-1 (MCP-1) and extracellular superoxide dismutase (EC‑SOD) were analyzed using nested touchdown-methylation-specific-polymerase chain reaction analysis. After 15 weeks, compared with the normal control group, serum concentrations of Hcy were significantly increased by 1.15‑, 2.54‑ and 1.17‑fold (P<0.05) in the ApoE‑/‑ control group, Meth group and Meth‑F group, respectively. The sizes of the atherosclerotic lesions were increased in the ApoE‑/‑ control group, Meth group and Meth‑F group, by up to 1.44‑, 2.40‑ and 1.45‑fold, respectively, compared with the normal control group (P<0.05). The concentrations of SAM were significantly increased by 3.02‑, 3.42‑ and 2.46‑fold in the ApoE‑/‑ control group, Meth group and Meth‑F group, respectively (P<0.05). The ratios of SAM/SAH were increased by 1.67‑ and 2.75‑fold in the in ApoE‑/‑ control group and Meth group, respectively, compared with the normal control group. The methylation levels of B1 repetitive elements, FABP4, MCP‑1 and EC‑SOD were decreased and exhibited hypomethylation. The methylation statuses of these genes were correlated with the ratio of the serum levels of SAM and SAH. These findings suggested that the SAM/SAH ratio is a biomarker and may provide a sensitive indicator for the clinical diagnosis of atherosclerosis.