Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3936-3942
Oxidative Modification of Low-Density Lipoprotein and
Atherogenetic Risk in 
-Thalassemia
M.A. Livrea,
L. Tesoriere,
A. Maggio,
D. D'Arpa,
A.M. Pintaudi, and
E. Pedone
From the Istituto di Farmacologia e Farmacognosia e Dipartimento di
Chimica e Tecnologie Farmaceutiche, Università di Palermo,
Palermo; and the Servizio Talassemia, Ospedale Cervello, Palermo.
Italy.
We investigated the oxidative state of low-density lipoprotein (LDL)
in patients with 
-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 -thalassemia intermedia
patients, aged 10 to 60, and compared with age-matched healthy
controls. Vitamin E and -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--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 -thalassemia patients. We suggest that the level of
plasma MDA in -thalassemia patients may represent a sensitive index
of the oxidative status of LDL in vivo and of its potential
atherogenicity.
