Livrea M A, Tesoriere L, Maggio A, D'Arpa D, Pintaudi A M, Pedone E
Istituto di Farmacologia e Farmacognosia e Dipartimento di Chimica e Tecnologie Farmaceutiche, Università di Palermo, Palermo; and the Servizio Talassemia, Ospedale Cervello, Palermo. Italy.
Blood. 1998 Nov 15;92(10):3936-42.
We investigated the oxidative state of low-density lipoprotein (LDL) in patients with beta-thalassemia to determine whether there was an association with atherogenesis. Conjugated diene lipid hydroperoxides (CD) and the level of major lipid antioxidants in LDL, as well as modified LDL protein, were evaluated in 35 beta-thalassemia intermedia patients, aged 10 to 60, and compared with age-matched healthy controls. Vitamin E and beta-carotene levels in LDL from patients were 45% and 24% of that observed in healthy controls, respectively. In contrast, the mean amount of LDL-CD was threefold higher and lysil residues of apo B-100 were decreased by 17%. LDL-CD in thalassemia patients showed a strong inverse correlation with LDL vitamin E (r = -0.784; P <.0001), while a negative trend was observed with LDL-beta-carotene (r = -0.443; P =.149). In the plasma of thalassemia patients, malondialdehyde (MDA), a byproduct of lipid peroxidation, was increased by about twofold, while vitamin E showed a 52% decrease versus healthy controls. LDL-CD were inversely correlated with plasma vitamin E (r = -0.659; P <.0001) and correlated positively with plasma MDA (r = 0.621; P <. 0001). Plasma ferritin was positively correlated with LDL-CD (r = 0.583; P =.0002). No correlation was found between the age of the patients and plasma MDA or LDL-CD. The LDL from thalassemia patients was cytotoxic to cultured human fibroblasts and cytotoxicity increased with the content of lipid peroxidation products. Clinical evidence of mild to severe vascular complications in nine of the patients was then matched with levels of LDL-CD, which were 36% to 118% higher than the mean levels of the patients. Our results could account for the incidence of atherogenic vascular diseases often reported in beta-thalassemia patients. We suggest that the level of plasma MDA in beta-thalassemia patients may represent a sensitive index of the oxidative status of LDL in vivo and of its potential atherogenicity.
我们研究了β地中海贫血患者低密度脂蛋白（LDL）的氧化状态，以确定其是否与动脉粥样硬化的发生有关。对35例年龄在10至60岁之间的中间型β地中海贫血患者的共轭二烯脂质氢过氧化物（CD）、LDL中主要脂质抗氧化剂的水平以及修饰的LDL蛋白进行了评估，并与年龄匹配的健康对照者进行比较。患者LDL中的维生素E和β-胡萝卜素水平分别为健康对照者的45%和24%。相比之下，LDL-CD的平均含量高出三倍，载脂蛋白B-100的赖氨酰残基减少了17%。地中海贫血患者的LDL-CD与LDL维生素E呈强负相关（r = -0.784；P <.0001），而与LDL-β-胡萝卜素呈负相关趋势（r = -0.443；P =.149）。在地中海贫血患者的血浆中，脂质过氧化的副产物丙二醛（MDA）增加了约两倍，而维生素E与健康对照者相比下降了52%。LDL-CD与血浆维生素E呈负相关（r = -0.659；P <.0001），与血浆MDA呈正相关（r = 0.621；P <.0001）。血浆铁蛋白与LDL-CD呈正相关（r = 0.583；P =.0002）。未发现患者年龄与血浆MDA或LDL-CD之间存在相关性。地中海贫血患者的LDL对培养的人成纤维细胞具有细胞毒性，且细胞毒性随脂质过氧化产物含量的增加而增加。然后将9例患者中轻度至重度血管并发症的临床证据与LDL-CD水平进行匹配，这些患者的LDL-CD水平比患者平均水平高36%至118%。我们的结果可以解释β地中海贫血患者中经常报道的动脉粥样硬化性血管疾病的发生率。我们认为，β地中海贫血患者的血浆MDA水平可能代表体内LDL氧化状态及其潜在动脉粥样硬化性的敏感指标。
