Intracellular homocysteine metabolites in SLE: plasma S-adenosylhomocysteine correlates with coronary plaque burden.

Intracellular homocysteine metabolites in SLE: plasma S-adenosylhomocysteine correlates with coronary plaque burden.
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DOI:
10.1136/lupus-2020-000453
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发表时间:
2021-01
影响因子:
3.9
通讯作者:
Petri MA
Petri MA
中科院分区:
医学3区
文献类型:
--
作者:
Stojan G;Li J;Liu T;Kane MA;Petri MA

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我们假设SLE患者的细胞内同型半胱氨酸和同型半胱氨酸代谢物水平与健康受试者的水平相比不成比例地升高,并且它们与SLE患者的冠状动脉斑块独立相关。采用液相色谱-串联质谱绝对定量分析法测定血浆和外周血单核细胞(PBMC)中的6种分析物:同型半胱氨酸(Hcy)、S-腺苷甲硫氨酸(SAM)、S-腺苷高半胱氨酸(SAH)、甲硫氨酸(Met)、胱硫醚(Cysta)和5-甲基四氢叶酸(5 m-THF)。然后,我们比较了10例SLE患者和10例年龄、性别和种族匹配的对照组的细胞内(PBMC)和细胞外(血浆)Hcy和Hcy代谢产物(SAM、SAH、Met、Cysta和5 m-THF)浓度。排除具有糖尿病、心血管疾病、高血压、每天饮酒超过3个单位、贫血、肾功能不全(血清肌酐>1.5 mg/dL)和妊娠史的受试者。所有SLE患者均进行了两次冠状动脉CT血管造影检查,以筛查隐匿性冠状动脉粥样硬化疾病。SLE患者血浆Hcy(p<0.0001)、SAH(p<0.05)、SAM(p<0.001)水平高于对照组,而Met(p<0.05)、Cysta(p<0.001)水平低于对照组。SLE患者PBMC细胞内Cysta(p<0.05)、SAH(p<0.05)、SAM(p<0.001)水平较高,5 m-THF水平较低(p<0.001)。血浆SAH与冠状动脉总斑块数、钙化斑块数、非钙化斑块数呈正相关(p<0.05)。尽管胞内Hcy水平相似,但SLE患者和对照组间Hcy代谢产物的胞内浓度存在显著差异。血浆SAH与冠状动脉总斑块数、钙化斑块数、非钙化斑块数呈正相关。
We hypothesised that intracellular homocysteine and homocysteine metabolite levels in patients with SLE are disproportionately elevated compared with the levels seen in healthy subjects and that they are independently associated with coronary plaque in SLE. A liquid chromatography–tandem mass spectrometry absolute quantification assay was used for the determination of six analytes in both plasma and peripheral blood mononuclear cells (PBMCs): homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), methionine (Met), cystathionine (Cysta) and 5-methyltetrahydrofolate (5m-THF). We then compared intracellular (PBMC) and extracellular (plasma) Hcy and Hcy metabolite (SAM, SAH, Met, Cysta and 5m-THF) concentrations in 10 patients with SLE and in 10 age, sex and ethnicity matched controls. Subjects with a history of diabetes mellitus, cardiovascular disease, hypertension, alcohol consumption in excess of 3 units per day, anaemia, renal insufficiency (serum creatinine >1.5 mg/dL) and pregnancy were excluded. All patients with SLE had two coronary CT angiography studies as screening for occult coronary atherosclerotic disease. Plasma from patients with SLE had higher levels of Hcy (p<0.0001), SAH (p<0.05), SAM (p<0.001) and lower levels of Met (p<0.05) and Cysta (p<0.001) compared with controls. PBMC intracellular concentrations from patients with SLE had higher levels of Cysta (p<0.05), SAH (p<0.05), SAM (p<0.001) and lower levels of 5m-THF (p<0.001). Plasma SAH showed a positive correlation with total coronary plaque, calcified plaque and non-calcified plaque (p<0.05). Intracellular concentrations of Hcy metabolites were significantly different between patients with SLE and controls, despite similar intracellular Hcy levels. Plasma SAH was positively correlated with total coronary plaque, calcified plaque and non-calcified plaque.
在喂食高膳食蛋氨酸的载脂蛋白 E 缺陷小鼠中,血浆 S-腺苷同型半胱氨酸是比同型半胱氨酸更好的动脉粥样硬化生物标志物。
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发表时间: 2008-02-01
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