Changes of serum paraoxonase (an HDL-cholesterol-associated lipophilic antioxidant) and arylesterase activities in severe preeclamptic women

Abstract

Objective: To determine the serum lipid profile, the activity of paraoxonase (PON, the lipophilic antioxidant component of HDL-cholesterol), and alterations of the arylesterase activity in preeclamptic women. Study Design: This cross-sectional study included 28 severe preeclamptic, and 24 healthy pregnant women. Fasting venous blood samples were collected during the antepartum period for spectrophotometric determination of the PON and arylesterase activities. Results: In the severe preeclamptic group, the mean levels of total cholesterol, triglycerides, and LDL-cholesterol were 4, 5 and 9.8% higher, respectively, and HDL-cholesterol 9% lower than in the healthy controls. The PON and arylesterase activities were significantly lower in the severe preeclamptic women than in the controls, P<0.001 and P=0.000, respectively. A moderately positive correlation was detected between the serum levels of HDL-cholesterol and PON (r=0.49, P<0.02, n=52) and between HDL-cholesterol and arylesterase (r=0.42, P<0.05, n=52). Conclusions: Our results suggest that an abnormal lipid profile and decreased PON and arylesterase activities may have a role in pathogenesis of preeclampsia.

Introduction

Preeclampsia is one of the most important diseases of pregnancy and is a major cause of maternal and fetal morbidity and mortality. Although it occurs in 4–5% of all pregnancies, the pathophysiology of this syndrome is not fully understood. Clinically, preeclampsia is characterized by hypertension and proteinuria [1]. Increasing clinical and biochemical evidences suggest that a disturbance of normal endothelial cell function may be a primary cause in the pathogenesis of preeclampsia [1], [2]. In classic studies, vascular lesions in the placental bed of women with preeclampsia were reported to be similar to atherosclerotic plaques [3]. It has been suggested that an abnormal lipid profile may have a role in the pathogenesis of preeclampsia [4]. The proposed mechanisms of lipid-mediated cardiovascular pathology in adults resemble those suggested for preeclampsia and chronic abnormal endothelial hyper-stimulation through lipid peroxidation have been suggested as precursors to dysfunction and damage [5]. Oxidation of LDL-cholesterol seems to be an important step in this process. Wakatsuki et al. suggested that oxidized LDL-cholesterol particles might be involved in vascular endothelial damage in preeclampsia [6].

Paraoxonase (PON) is a lipophilic antioxidant that is bound to HDL-cholesterol. It is a protein of 354 amino acids with a molecular mass of 43 kDa, present in serum and liver, which together with arylesterase has been demonstrated to function as a single enzyme [7], [8]. A recent hypothesis suggests an antioxidant role for PON in the protection of LDL-cholesterol from oxidative modifications [9]. To the best our knowledge the PON and arylesterase levels have not been studied as yet in preeclampsia. By assuming that PON and arylesterase activities might be decreased and that these antioxidant enzymes have a role in the pathogenesis of preeclampsia, we designed the present study to determine whether the PON and arylesterase activities were decreased or not in this disease.