Luka Suzuki1, Satoshi Hirayama2, Mariko Fukui3, Makoto Sasaki4, Sadayuki Hiroi5, Makoto Ayaori6, Shuji Terai7, Minoru Tozuka8, Hirotaka Watada1, Takashi Miida9. 1. Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan. 2. Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. 3. Department of General Thoracic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan. 4. Division of Anti-Aging and Vascular Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan. 5. Division of Pathology, Department of Clinical Laboratory Sciences, Nitobe Bunka College, Tokyo, Japan. 6. Tokorozawa Heart Center, Tokorozawa, Saitama, Japan. 7. Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata, Japan. 8. Analytical Laboratory Chemistry, Division of Biomedical Laboratory Sciences, Department of Moleculo-genetic Sciences, Tokyo Medical and Dental University Graduate School of Health Care Sciences, Tokyo, Japan. 9. Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: tmiida@juntendo.ac.jp.
Abstract
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.
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.
Authors: Lita A Freeman; Robert D Shamburek; Maureen L Sampson; Edward B Neufeld; Masaki Sato; Sotirios K Karathanasis; Alan T Remaley Journal: J Lipid Res Date: 2019-02-26 Impact factor: 5.922
Authors: Boris L Vaisman; Edward B Neufeld; Lita A Freeman; Scott M Gordon; Maureen L Sampson; Milton Pryor; Emily Hillman; Milton J Axley; Sotirios K Karathanasis; Alan T Remaley Journal: J Pharmacol Exp Ther Date: 2018-12-18 Impact factor: 4.030
Authors: Agnieszka Ćwiklińska; Agnieszka Mickiewicz; Robert Kowalski; Barbara Kortas-Stempak; Agnieszka Kuchta; Krzysztof Mucha; Michał Makowiecki; Anna Gliwińska; Krzysztof Lewandowski; Leszek Pączek; Marcin Fijałkowski; Marcin Gruchała; Maciej Jankowski Journal: J Med Biochem Date: 2020-09-02 Impact factor: 3.402
Authors: Edward B Neufeld; Lita A Freeman; Vinay Durbhakula; Maureen L Sampson; Robert D Shamburek; Sotirios K Karathanasis; Alan T Remaley Journal: Biology (Basel) Date: 2022-08-22
Authors: Marcelo J A Amar; Lita A Freeman; Takafumi Nishida; Maureen L Sampson; Milton Pryor; Boris L Vaisman; Edward B Neufeld; Sotirios K Karathanasis; Alan T Remaley Journal: Pharmacol Res Perspect Date: 2019-12-29