Tesoriere L, D'Arpa D, Maggio A, Giaccone V, Pedone E, Livrea M A
Istituto di Farmacologia e Farmacognosia, Università di Palermo, Italy.
Atherosclerosis. 1998 Apr;137(2):429-35. doi: 10.1016/s0021-9150(97)00300-6.
The alteration of the oxidant/antioxidant balance may affect the susceptibility of low density lipoproteins (LDL) to oxidation in haemolytic disorders such as thalassemia. Thirty patients affected by beta-thalassemia intermedia were examined, and compared with age-matched healthy controls. The mean amount of vitamin E in the thalassemic LDL was lower than control (p < 0.0001), either when it was calculated on the base of LDL protein (61% decrease) or cholesterol (25% decrease). The LDL resistance to Cu2+-induced oxidation, evaluated as the length of the lag phase before the onset of conjugated diene (CD) lipid hydroperoxide production, was 20% lower than control. Other parameters of LDL susceptibility to oxidation, such as the rate of lipid peroxidation, Rp, and the total amount of conjugated dienes produced, CDmax, were only slightly lower than control, which can be explained by a lower content of peroxidable lipids in the thalassemic LDL. Total LDL cholesterol was 1.08 x 10(3) and 2.07 x 10(3) mol/mol LDL in thalassemic and in control LDL, respectively. The length of the lag phase in thalassemic LDL shows a strongly positive correlation with its vitamin E content (r = 0.732; p < 0.0001). The r2-value of 0.53 provides evidence that more than 50% of the lag phase is determined by vitamin E. Oxidizability of LDL lipids may explain 22-24% of the lag phase, as calculated by the inverse correlation between the length of the lag phase and CDmax (r = -0.474; p = 0.008; r2 = 0.22) and Rp (r = -0.499; p = 0.005; r2 = 0.24). In multiple regression analysis, the lag phase was predictable to 66% by vitamin E plus CDmax, and to 60% by vitamin E plus Rp. Plasma vitamin E was 53% lower in thalassemia patients compared to control and positively correlated with vitamin E in the LDL (r = 0.677; p < 0.0001). None of the correlations above were observed in control subjects. In conclusion, beta-thalassemia is associated with very low levels of vitamin E in plasma and in LDL, a condition that renders these particles more susceptible to in vitro oxidative modification and may account for atherogenesis-related vascular diseases described in thalassemia. The present data on a statistically significant correlation between abnormally low vitamin E and oxidizability of LDL contribute substantially to the hypothesis that vitamin E is a pathophysiologically important determinant of antioxidative protection of LDL.
在诸如地中海贫血等溶血性疾病中，氧化剂/抗氧化剂平衡的改变可能会影响低密度脂蛋白（LDL）的氧化易感性。对30例中间型β地中海贫血患者进行了检查，并与年龄匹配的健康对照者进行了比较。无论是以LDL蛋白为基础计算（降低61%）还是以胆固醇为基础计算（降低25%），地中海贫血患者LDL中的维生素E平均含量均低于对照组（p<0.0001）。通过共轭二烯（CD）脂质过氧化氢产生前的延迟期长度评估，LDL对铜离子诱导氧化的抗性比对照组低20%。LDL氧化易感性的其他参数，如脂质过氧化速率Rp和产生的共轭二烯总量CDmax，仅略低于对照组，这可以用地中海贫血患者LDL中可过氧化脂质含量较低来解释。地中海贫血患者和对照组LDL中的总LDL胆固醇分别为1.08×10³和2.07×10³mol/mol LDL。地中海贫血患者LDL的延迟期长度与其维生素E含量呈强正相关（r=0.732；p<0.0001）。r²值为0.53表明延迟期的50%以上由维生素E决定。根据延迟期长度与CDmax（r=-0.474；p=0.008；r²=0.22）和Rp（r=-0.499；p=0.005；r²=0.24）的负相关计算，LDL脂质的氧化能力可解释延迟期的22%-24%。在多元回归分析中，维生素E加CDmax可预测延迟期的66%，维生素E加Rp可预测延迟期的60%。地中海贫血患者的血浆维生素E比对照组低53%，且与LDL中的维生素E呈正相关（r=0.677；p<0.0001）。在对照受试者中未观察到上述任何相关性。总之，β地中海贫血与血浆和LDL中极低水平的维生素E有关，这种情况使这些颗粒更容易受到体外氧化修饰，并可能解释了地中海贫血中描述的与动脉粥样硬化相关的血管疾病。关于异常低水平的维生素E与LDL氧化能力之间具有统计学显著相关性的当前数据，极大地支持了维生素E是LDL抗氧化保护的病理生理重要决定因素这一假说。
