Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation

Gerard Aragonès,Anabel García-Heredia,Marta Guardiola,Anna Rull,Raúl Beltrán-Debón,Judit Marsillach,Carlos Alonso-Villaverde,Bharti Mackness,Michael Mackness,Juan Pedro-Botet,Pedro Pardo-Reche,Jorge Joven,Jordi Camps

doi:10.1194/jlr.p018457

Abstract

We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. We studied 207 HIV-infected patients and 385 healthy volunteers. Serum PON3 was determined by in-house ELISA, and PON3 distribution in lipoproteins was investigated by fast-performance liquid chromatography (FPLC). Polymorphisms of the PON3 promoter were analyzed by the Iplex Gold MassArray(TM) method. PON3 concentrations were increased (about three times) in HIV-infected patients with respect to controls (P < 0.001) and were inversely correlated with oxidized LDL levels (P = 0.038). Long-term use of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy was associated with a decrease of PON3 concentrations. In a multivariate linear regression analysis, these relationships were still strong when the main confounding covariates were considered. PON3 was mainly found in HDL in HIV-infected patients, but a substantial amount of the protein was detected in LDL particles. This study reports for the first time an important increase in serum PON3 concentrations in HIV-infected patients that is associated with their oxidative status and their treatment with NNRTI. Long-term, prospective studies are needed to confirm the possible influence of this enzyme on the course of this disease and its possible utility as an analytical biomarker.

Highlights

We investigated the influence of the Human immunodeficiency virus (HIV) infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis
We have previously documented that serum paraoxonase-1 (PON1) activity and concentration are influenced by HIV infection [5] and that PON1 gene polymorphisms are related to the presence of subclinical atherosclerosis and CD4+ T-cell recovery following treatment [6]
Clinical research on PON3 has been hampered by the lack of methods for measurement, but we recently described a high-throughput, reliable enzyme-linked immunosorbent assay (ELISA) to analyze PON3 concentration in human serum [18]

Summary

Introduction

We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. This study reports for the first time an important increase in serum PON3 concentrations in HIV-infected patients that is associated with their oxidative status and their treatment with NNRTI. Human immunodeficiency virus (HIV)-infected patients often develop long-term metabolic alterations and concomitant atherosclerosis [1, 2]. We have previously documented that serum paraoxonase-1 (PON1) activity and concentration are influenced by HIV infection [5] and that PON1 gene polymorphisms are related to the presence of subclinical atherosclerosis and CD4+ T-cell recovery following treatment [6].

Objectives

Methods

Results