Serum Paraoxonase and Platelet-Activating Factor Acetylhydrolase in Chronic Renal Failure (Technical Briefs‪)‬

Human serum paraoxonase (aryldialkylphosphatase, EC 3.1.8.1; PON1) and human serum platelet-activating factor acetylhydrolase (1-alkyl-2-acetyl-glycero-phosphocholine esterase, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetohydrolase, EC 3.1.1.47; PAF-AH) are associated with HDL [1, 2]. PAF-AH is also found in LDL and lipoprotein(a) [Lp(a)] [3]. Recently, paraoxonase and PAF-AH have been shown to inhibit the oxidative modification of LDL [4, 5]. Furthermore, paraoxonase and PAF-AH can destroy active lipids in mildly oxidized LDL and hence may protect against the induction of inflammatory responses in arterial wall cells [6, 7]. Oxidation of LDL is recognized as a key early stage in the development of atherosclerosis, leading to uptake of LDL by the macrophage scavenger receptor and hence to formation of foam cells [8]. Thus, there is the potential for HDL-associated paraoxonase and PAF-AH to directly inhibit these processes. The PON1 gene has two common polymorphisms at amino acids 55 and 192 [9]. The 192 polymorphism leads to a Glu[right arrow]Arg substitution and results in two different isoforms that have high and low activity towards paraoxon as substrate [9, 10]. It has been suggested that paraoxonase and PAF-AH work in concert to detoxify lipid peroxides in LDL and may therefore have antiatherogenic properties [6]. Patients with chronic renal failure are at a greatly increased risk of developing cardiovascular disease. This is only partly explained by an increased prevalence of conventional risk factors [11, 12]. Increased susceptibility of LDL to oxidation has been reported in chronic renal failure [13, 14], although other studies have failed to confirm this finding [15, 16]. In view of the ability of HDL to protect LDL against oxidation, the aim of our study was therefore to investigate the activities of serum paraoxonase/arylesterase and PAF-AH in patients with chronic renal failure and hence to assess whether changes in activity might contribute to the accelerated development of atherosclerosis.