Prostaglandins, Leukotrienes and Essential Fatty Acids 72 (2005) 203–209 Lipoprotein-associated PAF-acetylhydrolase activity in subjects with the metabolic syndrome Evangelos Rizos a , Afroditi P. Tambaki b , Irene Gazi a , Alexandros D. Tselepis b,Ã , Moses Elisaf a a School of Medicine, Department of Internal Medicine, University of Ioannina, Dourouti Campus, 45110 Ioannina, Greece b Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece Received 15 September 2004; accepted 25 October 2004 Abstract Plasma- and lipoprotein-associated activity of the platelet activating factor acetylhydrolase (PAF-acetylhydrolase, PAF-AH) plays an important role in inflammation and in atherosclerotic process, which are present in the metabolic syndrome (MS). Paraoxonase 1 (PON1) is an esterase associated with high-density lipoprotein (HDL) which contributes to the anti-atherogenic effects of this lipoprotein. We investigated the activities of both enzymes in 60 patients with MS and 110 age- and sex-matched subjects without it (non-MS group). Plasma PAF-AH activity was higher in the MS compared to the non-MS group, while HDL–PAF-AH and serum PON1 activities were lower in the MS compared to the non-MS group. Univariate regression analysis in the MS group showed that plasma PAF-AH activity was positively associated with systolic blood pressure, whereas HDL–PAF-AH activity was inversely associated with the homeostasis model assessments (HOMA) index. Both associations remained significant in the multivariate regression analysis, suggesting that insulin resistance and systolic hypertension are major determinants for the alterations in plasma and HDL-associated PAF-AH activity among those observed in MS patients. r 2004 Elsevier Ltd. All rights reserved. 1. Introduction The metabolic syndrome (MS) comprises a distinct entity characterized by three or more of the following criteria: waist circumference 4102 cm in men and 488 cm in women, triglycerides 4150 mg/dl, high- density lipoprotein cholesterol (HDL-C) o40 mg/dl in men and o50 mg/dl in women, blood pressure X130/ 85 mm Hg and fasting glucose X110 mg/dl. In addition, a number of inflammatory factors as well as some abnormalities in haemostatic factors are encountered in patients with MS [1-7]. The importance of the MS is continuously growing, taking into account that in the United States 25% of adults older than 20 years and 45% older than 50 years are affected by this syndrome, while in Greece 25% of men and 15% of women older than 18 years have the MS [1,5,7,8]. Platelet activating factor acetylhydrolase (PAF-AH) is an enzyme that expresses a Ca 2+ -independent phospholipase A 2 activity and catalyzes the hydrolysis of the ester bond at the sn-2 position of the proin- flammatory phospholipid mediator platelet activating factor (PAF). PAF-AH also degrades oxidatively fragmented phospholipids, which are formed during the oxidative modification of low-density lipoprotein (LDL) and may play important roles in atherogenesis [9,10]. The PAF-AH activity in human plasma is mainly associated with LDL, whereas a small proportion of the enzyme activity is found to be related to HDL [10]. The role of plasma PAF-AH activity in atherosclerosis remains obscure, since anti-inflammatory and anti- atherogenic properties as well as pro-inflammatory and ARTICLE IN PRESS www.elsevier.com/locate/plefa 0952-3278/$ - see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.plefa.2004.10.021 Ã Corresponding author. Tel.: +30 2651 098 365; fax: +30 2651 047 832. E-mail address: atselep@cc.uoi.gr (A.D. Tselepis).