期刊
JOURNAL OF CLINICAL LIPIDOLOGY
卷 7, 期 2, 页码 109-116出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2012.08.001
关键词
ABCA1; ABCG1; Cholesterol efflux; Familial hypercholesterolemia; LDL apheresis; SR-BI
资金
- Throne-Hoist Foundation, Oslo, Norway
- Norwegian Association of Heart and Lung Patients, Oslo, Norway
- Johan H. Andresen Medical Foundation, University of Oslo, Norway
- Kaneka Phaxma Europa N.V., Germany
BACKGROUND: Homozygous familial hypercholesterolemia (FH) is a rare disorder that may affect 1 person per million. Early initiation of aggressive cholesterol-lowering therapy is essential to prevent premature coronary heart disease. Selective removal of low-density lipoprotein (LDL) by LDL apheresis is a reliable method of treatment. METHODS AND RESULTS: Cholsterol efflux mediators of homozygous FH patients on weekly LDL apheresis were compared with those of age- and sex-matched heterozygous FH patients receiving oral medication only and with healthy control subjects. The data show that (1) compared with healthy controls, homozygous FH patients have significantly lower plasma levels of high-density lipoprotein cholesterol and apoA-I and significantly lower cholesterol-acceptor capacity of serum to promote cholesterol efflux from cholesterol-loaded THP-1 cells, combined with significantly lower peripheral blood mononuclear cell gene expression levels of ATP-binding cassette (ABC) transporter G1 and borderline-significantly lower levels of ABCA1 and scavenger receptor class B type I (SR-BI); and (2) compared with pre-LDL apheresis (a day before treatment), postapheresis (15 days later; on the day after the weekly treatment) levels of HDL cholesterol and apoA-I were significantly reduced, with no significant effect on cholesterol-acceptor capacity of serum or on peripheral blood mononuclear cell gene expression levels of the cellular transporters, except for a borderline-significant reduction in ABCA1 mRNA levels. CONCLUSIONS: The data showing decreased levels of cholesterol efflux mediators in plasma and cells may suggest that the overall cholesterol efflux capacity is impaired in homozygous FH patients. However, LDL apheresis may maintain cholesterol efflux capacity, despite a lowering levels of highdensity lipoprotein cholesterol and apoA-I. (C) 2013 National Lipid Association. All rights reserved.
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