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Journal of Lipid Research, Vol 28, 540-548, Copyright © 1987 by Lipid Research, Inc.
Y Kleinman, G Schonfeld, D Gavish, Y Oschry and S Eisenberg
Low density lipoproteins (LDL) of untreated moderate to severe
hypertriglyceridemic patients (HTG-LDL) are smaller in size and are
relatively enriched in triglycerides and proteins compared with normal LDL
(N-LDL). HTG-LDL also manifest defective binding to the LDL receptors of
normal cultured human fibroblasts. These structural and functional defects
are reversible by effective hypolipidemic therapy. The aims of the present
study were to confirm the reversibility of the structural and functional
defects in mild to moderate hypertriglyceridemic patients and also to test
the hypothesis that therapy improved the binding of HTG-LDL to cells by
modulating epitopes of apolipoprotein B (apoB-100) on the surfaces of LDL
particles. Fasting plasma samples were obtained from five mild to moderate
hypertriglyceridemic patients before and 3 weeks after bezafibrate therapy
when mean triglyceride levels were 436 and 157 mg/dl (P less than 0.01),
respectively. LDL particles were isolated by zonal ultracentrifugation,
characterized chemically, and assayed for cell association and proteolytic
degradation in-up regulated normal human skin fibroblasts. LDL
immunoreactivity was tested in solid phase competitive binding
radioimmunoassays (RIA) using three monoclonal antiLDL antibodies (Mab).
Mab 464B1B3 and Mab 465B6C3 react against epitopes in the COOH-terminal
(T2/K4) fragment of apoB-100. Mab D7.1 reacts with an epitope in the
midportion (T3/K3) fragment. Mab 464B1B3 inhibits the binding of LDL to the
LDL receptor. Hypolipidemic treatment altered the composition of LDL. Mean
LDL triglycerides fell from 9.4 to 5.8% of LDL mass (P less than
0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Hypolipidemic therapy modulates expression of apolipoprotein B epitopes on low density lipoproteins. Studies in mild to moderate hypertriglyceridemic patients
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