Oxidative structural modifications of low density lipoprotein in homozygous familial hypercholesterolemia

Claudio Napoli, Alfredo Postiglione, Massimo Triggiani, Gaetano Corso, Giuseppe Palumbo, Virginia Carbone, Antonio Ruocco, Giuseppe Ambrosio, Silvana Montefusco, Antonio Malorni, Mario Condorelli, Massimo Chiariello

Research output: Contribution to journalArticle

Abstract

Patients with homozygous familial hypercholesterolemia (FH), as a result of the increased levels and prolonged residence time of low density lipoprotein (LDL) in plasma, have a strong tendency toward accumulation of LDL-cholesterol in the arterial wall, causing premature atherosclerosis. This phenomenon may enhance per se the physiological degradation of both protein and lipid component of LDL, which be more susceptible to oxidative damage induced by oxygen radicals. It is well known that LDL may undergo oxidative modification before being taken up by macrophages which are then transformed into foam cells. It has been suggested that platelet-activating factor (PAF) may play an important role in atherogenesis and PAF catabolism is known to be mediated by serum acetylhydrolase, an enzyme that is normally associated with LDL. Thus, the present study was designed to investigate the structural properties of LDL, including acetylhydrolase activity, in homozygous FH as compared to normolipidemic subjects before and after xanthine/xanthine oxidase-mediated oxidation. We studied 8 homozygous FH patients matched with 8 normolipidemic volunteers. Lipids of LDL fraction were extracted and verified by thin layer chromatography (TLC) analysis. Fatty acids were methylated and injected into a gas chromatograph/mass spectrometer. Vitamin E in LDL was determined by high performance liquid chromatography (HPLC). As an index of susceptibility of LDL to oxidative modifications, the formation of lipid-conjugated dienes was continuously monitored at 234 nm. Lipid peroxidation was also evaluated from the amount of both lipid peroxides (LPO) and malonyldialdehyde (MDA) content. Apolipoprotein (apo) B-100 on LDL was carried on polyacrylamide and agarose gel electrophoresis. In the homozygous FH patients, the relative content of cholesteryl ester was slightly increased.

Original languageEnglish
Pages (from-to)259-273
Number of pages15
JournalAtherosclerosis
Volume118
Issue number2
DOIs
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Napoli, C., Postiglione, A., Triggiani, M., Corso, G., Palumbo, G., Carbone, V., Ruocco, A., Ambrosio, G., Montefusco, S., Malorni, A., Condorelli, M., & Chiariello, M. (1995). Oxidative structural modifications of low density lipoprotein in homozygous familial hypercholesterolemia. Atherosclerosis, 118(2), 259-273. https://doi.org/10.1016/0021-9150(95)05612-2