Abstract
To investigate the potential determinants of the pleiotropic effects of statins, we
measured NK cell cytotoxicity in samples from normal subjects and patients, including
patients receiving statin therapy. In a multivariate analysis, NK cell cytotoxicity
was related to total plasma cholesterol concentration rather than statin use. In vitro, we investigated the role of lipid modification, specifically the effects on membrane
rafts and raft-dependent signal transduction. We demonstrate that statins reduce NK
cell cytotoxicity and that membrane cholesterol depletion by cyclodextrins has a similar
effect. In contrast, isoprenyl transferase inhibitors had little or no effect on NK
cell function. We hypothesise that the pleiotropic effects of statins reflect changes
in membrane cholesterol and, specifically, the density of membrane rafts. Moreover,
there is likely to be a relationship between membrane cholesterol, membrane rafts
and cell function that may be involved in the pathogenesis of cardiovascular and metabolic
diseases.
Keywords
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Article info
Publication history
Published online: June 29, 2006
Accepted:
May 22,
2006
Received in revised form:
May 19,
2006
Received:
February 3,
2006
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
