Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels
Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels
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DOI：
10.1161/01.atv.19.5.1263
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发表时间：
1999-05-01
影响因子：
8.7
通讯作者：
Salonen, JT
中科院分区：
文献类型：
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作者：
Voutilainen, S;Morrow, JD;Salonen, JT
血浆总同型半胱氨酸（tHcy）水平升高被认为是动脉粥样硬化的独立危险因素。高同型半胱氨酸血症诱导动脉粥样硬化的机制尚不完全清楚，但已提出促进LDL氧化和内皮损伤。本研究的目的是检验这一假设，即高血浆tHcy与男性体内脂质过氧化增加有关，通过血浆F-2-异前列烷浓度测定。我们在动脉粥样硬化预防（ASAP）研究中的抗氧化剂补充剂参与者中调查了这种关联。在256名男性参与者中，选择100名连续男性的子样本进行F-2-异前列烷测定。平均tHcy为11.0 μ mol/L，平均F-2-异前列腺素为29.6 ng/L。血浆tHcy与F-2-异前列腺素的相关系数为0.40（P < 0.001）。在线性回归模型中，与F-2-异前列烷相关性最强的变量是tHcy（标准化系数0.33，P < 0.001），血清甘油三酯（0.21，P = 0.042），缺糖转铁蛋白（0.15，P = 0.132）和血浆脂质标准化α-生育酚（-0.11，P = 0.252）（模型的R-2 = 0.24，P < 0.001）。血浆F-2-异前列腺素水平在tHcy的五分位数之间呈线性增加（P < 0.001）。最高tHcy五分位数（37.4，31.1 - 43.6 ng/L）中的F-2-异前列腺素未校正平均值（95%置信区间）比最低五分位数（25.3，21.3 - 29.3 ng/L）高47.5%。调整F-2-异前列烷的最强其他决定因素后，该差异降至28.2%（P = 0.010）。我们目前的数据表明，空腹血浆tHcy升高与男性体内脂质过氧化增强有关。
An elevated plasma total homocysteine level (tHcy) is considered an independent risk factor for atherosclerosis, The mechanisms by which hyperhomocysteinemia induces atherosclerosis are only partially understood, but promotion of LDL oxidation and endothelial injury have been suggested. The purpose of this study was to test the hypothesis that a high plasma tHcy is associated in men with increased in vivo lipid peroxidation, as measured by plasma F-2-isoprostane concentrations. We investigated this association in a subset of the participants in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. Of 256 male participants, a subsample of 100 consecutive men was selected for F-2-isoprostane assays. The mean tHcy was 11.0 mu mol/L, and the mean F-2-isoprostanes was 29.6 ng/L. The simple correlation coefficient for association between tHcy and F-2-isoprostane was 0.40 (P < 0.001). In a linear regression model, the variables with the strongest associations with F-2-isoprostane were tHcy (standardized coefficient 0.33, P < 0.001), serum triglycerides (0.21, P = 0.042), carbohydrate-deficient transferrin (0.15, P = 0.132), and plasma lipid-standardized alpha-tocopherol (-0.11, P = 0.252) (R-2 = 0.24, P < 0.001 for model). Plasma F-2-isoprostane levels increased linearly across quintiles of tHcy (P < 0.001), The unadjusted mean (95% confidence interval) F-2-isoprostanes was 47.5% greater in the highest tHcy quintile (37.4, 31.1 to 43.6 ng/L) than in the lowest quintile (25.3, 21.3 to 29.3 ng/L). Adjustment for the strongest other determinants of F-2-isoprostane reduced this difference to 28.2% (P = 0.010). Our present data suggest that elevated fasting plasma tHcy is associated with enhanced in vivo lipid peroxidation in men.