Reduced Paraoxonase1 Activity Is a Risk for Atherosclerosis in Patients with Systemic Lupus Erythematosus

Authors: KISS, EMESE¹; SERES, ILDIKÓ²; TARR, TÜNDE¹; KOCSIS, ZSOLT¹; SZEGEDI, GYULA¹; PARAGH, GYÖRGY²

Source: Annals of the New York Academy of Sciences, Volume 1108, Number 1, June 2007 , pp. 83-91(9)

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Abstract:

Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonase1 (PON1) and arylesterase activities, and lipid-profile in 37 SLE patients and 30 age-/sex-matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti-oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 ± 13.9 year, follow-up time 6.7 ± 6.2 year, SLEDAI 2 (0-15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured anti-oxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 ± 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 ± 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL-C, HDL-C, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti-PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL-subfractions or enzyme abnormalities in HDL remodeling.

Keywords: SLE; paraoxonase1; atherosclerosis; antioxidant

Document Type: Research article

DOI: http://dx.doi.org/10.1196/annals.1422.009

Affiliations: 1: Third Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary 2: First Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

Publication date: 2007-06-01

Reduced Paraoxonase1 Activity Is a Risk for Atherosclerosis in Patients with Systemic Lupus Erythematosus

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