Divergent Effects of α-Tocopherol and Vitamin C on the Generation of Dysfunctional HDL Associated with Diabetes and the Hp 2-2 Genotype
Divergent Effects of α-Tocopherol and Vitamin C on the Generation of Dysfunctional HDL Associated with Diabetes and the Hp 2-2 Genotype
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DOI：
10.1089/ars.2009.2829
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发表时间：
2010-01-01
影响因子：
6.6
通讯作者：
Levy, Andrew P.
中科院分区：
文献类型：
--
作者：
Asleh, Rabea;Levy, Andrew P.
结合珠蛋白（Hp）2-2基因型与糖尿病（DM）患者心血管疾病（CVD）风险增加相关。我们最近提出，这种增加的风险来自于氧化还原活性血红蛋白（Hb）与高密度脂蛋白（HDL）的结合，从而导致HDL的氧化修饰。临床试验表明，维生素E（α-生育酚）降低，而维生素C增加心血管疾病的Hp 2-2糖尿病患者。我们试图检验这一假设，即α-生育酚或维生素C对Hp 2-2 DM CVD的相互作用是由于它们对HDL氧化和功能的不同影响。维生素C显着增加，而α-生育酚完全阻断氧化介导的糖基化Hb-Hp 2-2。维生素C没有任何益处，而α-生育酚完全恢复了Hp 2-2 DM小鼠的HDL功能。维生素C的联合给药减轻了α-生育酚对HDL的保护作用。维生素C和α-生育酚与Hp 2-2基因型对HDL功能和结构的影响存在药物基因组学相互作用。在正确的患者亚群中选择正确的抗氧化剂可能是关键，以证明抗氧化剂治疗的益处。抗氧化剂。氧化还原信号。12，209-218.
The haptoglobin (Hp) 2-2 genotype is associated with increased risk of cardiovascular disease (CVD) in diabetes (DM). We recently proposed this increased risk arises from the tethering of redox active hemoglobin (Hb) to high density lipoprotein (HDL), thereby resulting in oxidative modification of HDL. Clinical trials have demonstrated that vitamin E (alpha-tocopherol) decreases while vitamin C increases CVD in Hp 2-2 DM individuals. We sought to test the hypothesis that the interaction of alpha-tocopherol or vitamin C on CVD in Hp 2-2 DM was due to their divergent effects on HDL oxidation and function. Vitamin C significantly increased while alpha-tocopherol completely blocked oxidation mediated by glycosylated Hb-Hp 2-2. Vitamin C had no benefit while alpha-tocopherol completely restored HDL function in Hp 2-2 DM mice. Co-administration of vitamin C mitigated the protective effects of alpha-tocopherol on HDL. There exists a pharmacogenomic interaction between vitamin C and alpha-tocopherol and the Hp 2-2 genotype on HDL function and structure. Choosing the correct antioxidant in the correct subset of patients may be critical in order to demonstrate benefit from antioxidant therapy. Antioxid. Redox Signal. 12, 209-218.