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Lipoprotein-X in cholestatic patients causes xanthomas and promotes foam cell formation in human macrophages
Luka Suzuki1, Satoshi Hirayama2, Mariko Fukui3
1Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Background:
Lipoprotein-X (Lp-X) is an abnormal phospholipid-rich lipoprotein found in patients with cholestatic liver disease. Some patients exhibit skin xanthomas and severe hyperlipidemia.
Objective:
We investigated whether Lp-X induces foam cell formation in human-derived macrophages.
Methods:
To compare the atherogenic properties of Lp-X and modified LDL, we isolated Lp-X from 2 patients who had drug-induced cholestasis and xanthoma striata in the interphalangeal folds. We prepared oxidized LDL and acetylated LDL from healthy volunteers for the positive control experiments.
Results:
When human monocyte-derived macrophages were incubated with these lipoproteins, the isolated Lp-X induced more prominent lipid accumulation than oxidized LDL or acetylated LDL. One case underwent liver biopsy, with the bile ducts showing marked damage, fulfilling the criteria for vanishing bile duct syndrome. The other case was clinically diagnosed as drug-induced hypersensitivity syndrome. In both cases, Lp-X levels decreased markedly and the xanthomas disappeared completely after the improvement of cholestasis.
Conclusion:
This study indicates that Lp-X induces foam cell formation in human-derived macrophages. Our findings strongly suggest that persistently elevated Lp-X may cause xanthomas.