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Kafonek SD, Raikhel I, Bachorik PS, et al. Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages. Atherosclerosis. 1993;102(1):23-36doi: 10.1016/0021-9150(93)90081-5.
Kafonek, S. D., Raikhel, I., Bachorik, P. S., & Kwiterovich, P. O. (1993). Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages. Atherosclerosis, 102(1), 23-36. https://doi.org/10.1016/0021-9150(93)90081-5
Kafonek, S D, et al. "Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages." Atherosclerosis vol. 102,1 (1993): 23-36. doi: https://doi.org/10.1016/0021-9150(93)90081-5
Kafonek SD, Raikhel I, Bachorik PS, Kwiterovich PO. Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages. Atherosclerosis. 1993 Aug;102(1):23-36. doi: 10.1016/0021-9150(93)90081-5. PMID: 8257450.
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Elsevier Science

Atherosclerosis. 1993 Aug;102(1):23-36. doi: 10.1016/0021-9150(93)90081-5.

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

Atherosclerosis

S D Kafonek, I Raikhel, P S Bachorik, P O Kwiterovich

Affiliations

  1. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

PMID: 8257450 DOI: 10.1016/0021-9150(93)90081-5

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.

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