© 1996 American Heart Association, Inc.
Articles |
A Cytotoxic Electronegative LDL Subfraction Is Present in Human Plasma
From the Laboratoire de Biochimie, Hôpital Broussais, Paris (K.D., I.M., B.V., N.M.); the Laboratoire de Biochimie Appliquée, Faculté des Sciences Pharmaceutiques et Biologiques, Châtenay-Malabry (K.D., I.M., B.C., B.V., M.A.P.-A., N.M.), France; and the University of California at Los Angeles, School of Medicine (M.E.H.).
Correspondence to Dr Karine Demuth, Laboratoire de Biochimie Appliquée (tour D4, 2ème étage), Faculté des Sciences Pharmaceutiques et Biologiques, 5 rue J.B. Clément, F-92296 Châtenay-Malabry Cedex, France.
Abstract By using fast protein liquid chromatography, we isolated from human plasma a minor electronegative LDL subfraction designated LDL(-). After immunoaffinity chromatography against apolipoprotein (apo)(a) and apo A-I, LDL(-) represented 6.7±0.9% (mean±SD; n=18) of total LDL. Compared with the major LDL subfraction, designated LDL(+), LDL(-) contained similar amounts of thiobarbituric acid–reactive substances, conjugated dienes, and vitamin E and had a similar lipid/protein ratio and mean density. Moreover, the apo B of LDL(-) was not aggregated and its LDL receptor–binding activity was slightly increased. These results were consistent with the nonoxidized nature of LDL(-). LDL(-) showed increased contents of sialic acid (38.1±5.2 versus 28.9±3.3 nmol/mg protein; n=7; P<.01), apo C-III (1.43±0.21% versus 0.14±0.04%; n=7; P<.01), and apo E (1.64±0.26% versus 0.10±0.05%; n=7; P<.0005). Compared with LDL(+), LDL(-) displayed enhanced cytotoxic effects on cultured human umbilical vein endothelial cells, as shown by lactate dehydrogenase assay (P<.003; n=6), neutral red uptake (P<.02; n=6), and morphological studies. We also studied the relationship of LDL(-) to age and plasma lipid levels in 133 subjects. The percentage of contribution of LDL(-) to total plasma LDL correlated with age (P<.05), total cholesterol (P<.05), and LDL cholesterol (P<.003). In conclusion, this study shows that LDL(-), a circulating human plasma LDL, is an electronegative native LDL subfraction with cytotoxic effects on endothelial cells. This subfraction, which correlates positively with common atherosclerotic risk factors, might induce atherogenesis by actively contributing to alteration of the vascular endothelium.
Key Words: low-density lipoprotein • electronegativity • atherosclerotic risk factors • cytotoxicity • human umbilical vein endothelial cell
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