Simvastatin inhibits lymphocyte function in normal subjects and patients with cardiovascular disease

Hillyard, D.Z., Cameron, A.J.M., McDonald, K.J., Thomson, J., MacIntyre, A., Shiels, P.G. , Panarelli, M. and Jardine, A.G. (2004) Simvastatin inhibits lymphocyte function in normal subjects and patients with cardiovascular disease. Atherosclerosis, 175(2), pp. 305-313. (doi:10.1016/j.atherosclerosis.2004.03.018)

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Abstract

HMG-CoA reductase inhibitors (statins) block the mevalonate pathway, preventing biosynthesis of cholesterol and isoprenoids. We investigated the effect of simvastatin on lymphocytes from normal human subjects and cardiovascular disease patients in order to provide a model for the in vivo actions of statins. Thirteen healthy volunteers were treated with 40 mg per day of simvastatin following which mean total cholesterol was reduced by 23% (S.D.±11.7%) and mean LDL-cholesterol by 36% (S.D.±16.3%). Lymphocyte lipid raft levels, represented by Lyn and Fyn, were also reduced by simvastatin. Treatment with simvastatin did not alter ex vivo T-lymphocyte proliferation. However, the in vitro addition of 1 μM simvastatin reduced T-lymphocyte proliferation by 39% (S.D.±18.1%) and a combination of prenyl transferase inhibitors reduced proliferation by 19% (S.D.±22.7%). We also assessed the cytotoxicity of natural killer (NK) cells—a T-lymphocyte subset. NK cell cytotoxicity ex vivo was reduced by 30% (S.D.±33.6%) following oral simvastatin treatment and by 56% (S.D.±24.68%) after the in vitro addition of 1 μM simvastatin. Significant ex vivo reductions in T-cell proliferation and NK cell cytotoxicity were observed in patients with cardiovascular disease on treatment with statins. NK cells have been implicated in the pathogenesis of atherosclerosis, so the effect of statin therapy on NK cell cytotoxicity may contribute to the benefits of statins in cardiovascular disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McDonald, Dr Kenneth and Shiels, Professor Paul and Hillyard, Ms Dianne and Jardine, Professor Alan
Authors: Hillyard, D.Z., Cameron, A.J.M., McDonald, K.J., Thomson, J., MacIntyre, A., Shiels, P.G., Panarelli, M., and Jardine, A.G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Atherosclerosis
Publisher:Elsevier Ireland Ltd
ISSN:0021-9150
ISSN (Online):1879-1484
Published Online:10 May 2004

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