当前位置： SCI文献检索 > ATHEROSCLEROSIS期刊下所有文献 > Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages.

Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages.

Abstract：

:Hyperapobetalipoproteinemia (hyperapo B), a common disorder associated with coronary artery disease, is characterized by an increased number of small, dense, low density lipoprotein (LDL) particles. The cellular mechanisms responsible for early atherosclerosis in hyperapo B are unknown. We tested the hypothesis that hyperapo B LDL may be preferentially metabolized through an LDL receptor independent pathway promoting the accumulation of cellular cholesteryl ester (CE). THP-1 macrophages have little inducible LDL receptor activity after differentiation with phorbol esters and are, therefore, suitable for assessing non-LDL receptor mediated uptake of lipoproteins. LDL isolated from hyperapo B donors was found to have significantly lower total cholesterol to protein ratio (P = 0.03), higher average density (P = 0.0001) and smaller particle diameter (P = 0.016) compared with normal (control) LDL. LDL (250 micrograms lipoprotein-protein/ml) from normal (n = 11) and hyperapo B (n = 18) subjects were incubated for 24 h with THP-1 macrophages. The mean (S.D.) CE accumulation was 6.2 (3.6) for the normal and 6.4 (2.6) for the hyperapo B LDL (P = 0.84). CE accumulation in cells incubated with malondialdehyde modified (MDA) LDL, or without added lipoprotein, was 18.2 (2.0) and 0.6 (0.7), respectively. CE mass accumulation was significantly correlated with time (6-48 h) of incubation and concentration (100-500 micrograms/ml) of LDL protein (P < 0.05); no differences were observed between normal and hyperapo B LDL. Similarly, when the major LDL species was isolated by density gradient ultracentrifugation, mean (S.D.) CE was similar for the normal and hyperapo B LDL (8.7 (1.2) vs. 6.9 (1.5)). There were no differences in the mean (S.D.) incorporation of [14C]oleate into CE (nmol/mg cell protein per 6 h) in THP-1 macrophages incubated with normal or hyperapo B LDL (0.238 (0.045) vs. 0.211 (0.046)); results were comparable in human monocyte-derived (HMD) macrophages (0.298 (0.037) vs. 0.258 (0.022)). Also, mean (S.D.) cellular uptake and degradation (ng 125I/mg cell protein per h) in THP macrophages of normal and hyperapo B LDL were similar (uptake: 18 (14) vs. 12 (6.0); degradation: 58 (32) vs. 44 (8)). In summary: (1) hyperapo B LDL did not stimulate the accumulation of cellular CE via LDL receptor independent pathways in THP-1 macrophages, (2) normal and hyperapo B LDL stimulation of CE synthesis is similar in THP-1 and HMD macrophages and (3) no differences in cellular uptake and degradation of normal and hyperapo B LDL were observed in THP macrophages.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Kafonek SD,Raikhel I,Bachorik PS,Kwiterovich PO Jr

doi

10.1016/0021-9150(93)90081-5

subject

Has Abstract

pub_date

1993-08-01 00:00:00

pages

23-36

issue

eissn

0021-9150

issn

1879-1484

pii

0021-9150(93)90081-5

journal_volume

102

pub_type

杂志文章

在线工具

Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages.