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
Cholesterol 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 high-density lipoprotein cholesterol and apoA-I.
Keywords
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Article info
Publication history
Published online: August 10, 2012
Accepted:
August 1,
2012
Received:
May 21,
2012
Identification
Copyright
© 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.
