Free radical-induced lipid peroxidation associated with a decrease in plasma antioxidant capacity and UA levels as well as altered hepatic function is observed after deflation of the pneumoperitoneum. These results suggest that free radicals are generated at the end of a laparoscopic procedure, possibly as a result of an ischemia-reperfusion phenomenon induced by the inflation and deflation of the pneumoperitoneum.

Abstract-Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A 2 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 (nϭ55) or type IIB (nϭ21) 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 Ⅲ monocytes/macrophages Ⅲ platelet-activating factor acetylhydrolase Ⅲ paraoxonase Ⅲ atorvastatin P latelet-activating factor (PAF) is a potent lipid mediator involved in inflammatory diseases 1 as well as in atherogenesis. 2 In plasma, PAF is hydrolyzed and inactivated by PAF-acetylhydrolase (PAF-AH, EC 3.1.1.47), a Ca 2ϩ -independent phospholipase A 2 . 3 PAF-AH has a marked preference for phospholipids with short-chain moieties at the sn-2 position, and with the exception of PAF, PAF-AH can equally hydrolyze oxidized phospholipids containing a polyunsaturated fatty acyl residue at this position. 3 Plasma PAF-AH is complexed to lipoproteins 4,5 ; thus, it is also denoted as lipoprotein-associated phospholipase A 2 . 6 The role of this enzyme in inflammatory and atherosclerotic diseases remains to be established. Indeed, PAF-AH may represent a potent anti-inflammatory and antiatherogenic enzyme because it degrades PAF and proinflammatory oxidized phospholipids, molecules formed during the oxidation of LDL. 7 Consistent with the hypothesis that PAF-AH may exert a cardioprotective role are clinical studies showing that loss of plasma PAF-AH activity due to a G9943 T mutation in the PAF-AH gene may constitute a genetic determinant of atherosclerotic disease in the Japanese population. 8 In contrast to these findings, PAF-AH may exert proinflammatory and proatherogenic actions as a result of the hydrolysis of oxidized phospholipids, because bioactive oxidized free fatty acids 6 and lysophosphatidylcholine are generated. 9,10 A recent clinical study indicating that the mass of plasma PAF-AH could be a potential risk factor for coronary a...

Objective-Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) 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-PLA 2 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-PLA 2 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-PLA 2 on dense LDL subfraction (LDL-5 Key Words: hyperlipidemia Ⅲ lipoproteins Ⅲ PAF-acetylhydrolase Ⅲ Lp-PLA 2 Ⅲ ezetimibe Ⅲ fenofibrate Ⅲ rosuvastatin P latelet-activating factor (PAF) acetylhydrolase exhibits a Ca 2ϩ -independent phospholipase A 2 activity and degrades PAF and oxidized phospholipids by catalyzing the hydrolysis of the ester bond at the sn-2 position. 1 PAF-acetylhydrolase in plasma is complexed to lipoproteins 2 ; thus it is also referred as lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). 3 Lp-PLA 2 is associated mainly with apolipoprotein B (apoB)-containing lipoproteins and primarily with low-density lipoprotein (LDL), whereas a small proportion of circulating enzyme activity is also associated with high-density lipoprotein (HDL). 1,2 ⌻he majority of the LDL-associated Lp-PLA 2 activity is bound to the atherogenic small-dense LDL (sdLDL) particles, 2,4,5 and we recently showed that the enzyme activity is a marker of sdLDL particles in plasma. 6 Lp-PLA 2 is principally produced by hematopoietic cells including monocytes-macrophages. 7,8 Lp-PLA 2 has been identified in atherosclerotic plaques 9 ; however, its role in atherosclerosis is still under investigation. In this regard, it is suggested that this enzyme might have an antiinflammatory role because it degrades and inactivates proinflammatory PAF and oxidized phospholipids 10,11 ; other studies showed that Lp-PLA 2 may have a proinflammatory and proatherogenic role 12 because it generates lysophosphatidylcholine (lysoPC) 3,13 and bioactive oxidized fatty residues. 3 Data from large White population studies demonstrated an independent association between plasma Lp-PLA 2 with cardiovascular disease (CVD) risk. In this regard a recent metaanalysis showed that Lp-PLA 2 is significantly associated with CVD, and the risk estimate appears to be relatively unaffected by adjustment for conventional CVD risk factors. 14 In contrast to total plasma enzyme, which mainly represents ...

Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated mainly with the apolipoprotein B (apoB)-containing lipoproteins and primarily with LDL. A small proportion of enzymatic activity is also associated with HDL. Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL. The effect of fenofibrate on PAF-AH and PON1 activities in patients with dyslipidemias of Types IIA, IIB, and IV were studied. Fenofibrate reduced plasma PAF-AH activity in all patient groups. In Type IIA patients, this reduction was mainly due to a fall in enzyme activity associated with the dense LDL subspecies, whereas in Type IIB and Type IV patients, it was due to the decrease in PAF-AH activity associated with both the VLDL ؉ IDL and dense LDL subspecies. Drug therapy in Type IIB and Type IV patients significantly increased the HDL-associated PAF-AH activity due to the increase in enzyme activity associated with the HDL-3c subfraction. Fenofibrate did not affect serum PON1 activities toward paraoxon and phenylacetate in either patient group.The fenofibrate-induced elevation of HDL-associated PAF-AH activity in dyslipidemic patients of Type IIB and Type IV, as well as the reduction in enzyme activity associated with atherogenic apoBcontaining lipoproteins in all patient groups, may represent a new and important antiatherogenic effect of this potent lipid-modulating agent.

No abstract