doi: 10.1161/hq0202.102918
© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Atorvastatin Preferentially Reduces LDL-Associated Platelet-Activating Factor Acetylhydrolase Activity in Dyslipidemias of Type IIA and Type IIB
From the Departments of Internal Medicine (V.T., M.E.) and Cardiology (J.A.G.) and the Laboratory of Biological Chemistry (E.B.), Medical School, and the Laboratory of Biochemistry (S.-A.P.K., A.P.T., A.D.T.), Department of Chemistry, University of Ioannina, Ioannina, Greece, and the Institut National de la Santé et de la Recherche (M.J.C.), Unité 551, Hôpital de la Pitié, Paris, France.
Correspondence to Dr Alexandros D. Tselepis, Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. E-mail atselep{at}cc.uoi.gr
Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 that is primarily associated with low density lipoprotein (LDL). PAF-AH activity has also been found in high density lipoprotein (HDL), although it has recently been indicated that there is no PAF-AH protein in HDL. Plasma paraoxonase 1 (PON1) is an HDL-associated esterase, which also exhibits PAF-AH–like activity. The effect of atorvastatin (20 mg per day for 4 months) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA (n=55) or type IIB (n=21) was studied. In both patient groups, atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions (LDL-4 and LDL-5). Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group. However, because of the reduction in LDL cholesterol levels, the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration. The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin.
Key Words: hyperlipidemia • monocytes/macrophages • platelet-activating factor acetylhydrolase • paraoxonase • atorvastatin
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