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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2236.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A₂

Vasilios G. Saougos; Afroditi P. Tambaki; Mihalis Kalogirou; Michael Kostapanos; Irene F. Gazi; Robert L. Wolfert; Moses Elisaf; Alexandros D. Tselepis

From the Department of Internal Medicine, Medical School (V.G.S., M.Ka., M.Ko., I.F.G., M.E.), and the Laboratory of Biochemistry, Department of Chemistry (A.P.T., A.D.T.), University of Ioannina, Greece; and dia Dexus Inc (R.L.W.), South San Francisco, Calif.

Correspondence to Prof Alexandros D. Tselepis, Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. E-mail atselep{at}uoi.gr

Objective— Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a predictor for incident atherosclerotic disease. We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA₂ activity and mass.

Methods and Results— In 50 patients with Type IIA dyslipidemia were administered rosuvastatin (10 mg daily), whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy (10 mg daily). Fifty patients with Type IV dyslipidemia were given micronised fenofibrate (200 mg daily). Low- and high-density lipoprotein (LDL and HDL, respectively) subclass analysis was performed electrophoretically, whereas lipoprotein subfractions were isolated by ultracentrifugation. Ezetimibe reduced plasma Lp-PLA₂ activity and mass attributable to the reduction in plasma levels of all LDL subfractions. Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA₂ on dense LDL subfraction (LDL-5). Fenofibrate preferentially reduced the Lp-PLA₂ activity and mass associated with the VLDL+IDL and LDL-5 subfractions. Among studied drugs only fenofibrate increased HDL-associated Lp-PLA₂ (HDL-Lp-PLA₂) activity and mass attributable to a preferential increase in Lp-PLA₂ associated with the HDL-3c subfraction.

Conclusion— Ezetimibe, rosuvastatin, and fenofibrate reduce Lp-PLA₂ activity and mass associated with the atherogenic apoB-lipoproteins. Furthermore, fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA₂. The clinical implications of these effects remain to be established.

We investigated the effect of ezetimibe, rosuvastatin, and fenofibrate on the lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity and mass, in hyperlipidemic patients. All drugs reduced Lp-PLA₂ activity and mass associated with the atherogenic apoB-lipoproteins, whereas fenofibrate was the only drug that improved the specific activity of the enzyme associated with these lipoproteins and significantly induced the HDL–Lp-PLA₂. The clinical implications of these effects remain to be established.

Key Words: hyperlipidemia • lipoproteins • PAF-acetylhydrolase • Lp-PLA₂ • ezetimibe • fenofibrate • rosuvastatin

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