PON1, A New Biomarker of Cardiovascular Disease, Is Low in Patients with Systemic Vasculitis

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Objectives

Because systemic vasculitis (SV) predisposes to atherosclerosis, and high-density lipoprotein (HDL) prevents atherosclerosis by “reverse cholesterol transport” and by inhibiting low-density lipoprotein (LDL) oxidation thanks to apolipoprotein A-I (Apo-AI) and paraoxonase 1 (PON1), we assessed whether LDL oxidation was increased in SV and associated with less PON1 activity.

Methods

The sera of 33 patients with active SV (ASV), 32 in full remission of SV (RSV) and 20 healthy subjects (HS) were analyzed for C-reactive protein (CRP), high-sensitivity-CRP, lipids, lipoproteins, apolipoproteins, PON1 activity, LDL-immune complexes (LDL-IC), and auto-antibodies to oxidized-LDL (ox-LDL), and anticardiolipin antibodies.

Results

CRP was higher in ASV than RSV and HS, and negatively correlated with HDL-cholesterol and Apo-AI. Autoantibodies to ox-LDL and highly oxidized malondialdehyde-LDL were higher in RSV than ASV and HS (P < 0.05). LDL-IC titers were higher in ASV than RSV and HS (P < 0.05). PON1 activity was lower in ASV and RSV than HS (P = 0.02). A trend toward a negative correlation between basal PON1 activity and anti-MDA-LDL antibodies (P = 0.06) was observed.

Conclusion

Inflammatory markers in SV were associated with a modified lipoprotein profile, which could lower PON1 activity and contribute to increased ox-LDL titers and accelerated atherosclerosis development.

Section snippets

Patients

Thirty-three patients with active SV (ASV) (10 men, 23 women; mean ± SD age: 60.9 ± 15.7 years old) were included in the study. Exclusion criteria were the following: history of diabetes mellitus or hyperlipidemia; end-stage renal disease (ESRD; creatinine clearance, <30 mL/min), and/or statin or fibrate therapy. Twenty-one patients had small-vessel SV (Wegener’s granulomatosis [WG], n = 7, microscopic polyangiitis [MPA], n = 7, Churg–Strauss syndrome [CSS], n = 1, Henoch–Schönlein purpura

Results

The main demographic and biological characteristics of the tested populations are reported in Table 1. Plasma CRP levels were significantly higher in ASV patients than those in RSV or HS. Plasma HS-CRP of RSV patients was determined when CRP was undetectable (n = 22); they tended to be higher in patients in RSV than in HS. Creatininemia was significantly higher in RSV patients than those with ASV.

PON1 basal activity levels differed significantly among our 3 groups (ANOVA, P = 0.008) (Table 1).

Discussion

The results of our study show that aCL autoAb titers were higher in ASV patients than HS and that ox-LDL, MDA-LDL autoAb titers were higher in RSV than ASV patients or HS. Several authors reported that high autoAb titers to ox-LDL titers were associated with atherosclerosis, although some findings remain controversial (28, 29). Our results confirm the observations made by Swets and coworkers on 25 ASV patients (12), but it must be kept in mind that diabetes mellitus and ESRD have been reported

References (47)

  • J. Shepherd et al.

    Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial

    Lancet

    (2002)
  • T.R. Cupps et al.

    The vasculitic syndromes

    Adv Intern Med

    (1982)
  • E.M. Salisbury et al.

    Cardiovascular disease incidence and risks factors in ANCA-associated primary systemic vasculitis (AASV)

    Arthritis Rheum

    (2003)
  • T. Somer

    Thrombo-embolic and vascular complications in vasculitis syndromes

    Eur Heart J

    (1993)
  • A. Uddhammar et al.

    Increased mortality due to cardiovascular disease in patients with giant cell arteritis in northern Sweden

    J Rheumatol

    (2002)
  • G.S. Kerr et al.

    Takayasu’s arteritis

    Ann Intern Med

    (1994)
  • J.H. Qiao et al.

    Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice

    Arterioscler Thromb

    (1993)
  • R. Ross

    Atherosclerosis—an inflammatory disease

    N Engl J Med

    (1999)
  • W. Palinski et al.

    Low-density lipoprotein undergoes oxidative modification in vivo

    Proc Natl Acad Sci USA

    (1989)
  • C.R. Wang et al.

    Circulating intercellular adhesion molecules-1 and autoantibodies including anti-endothelial cell, anti-cardiolipin, and anti-neutrophil cytoplasma antibodies in patients with vasculitis

    Clin Rheumatol

    (1993)
  • B.P. Swets et al.

    Patients with systemic vasculitis have increased levels of autoantibodies against oxidized LDL

    Clin Exp Immunol

    (2001)
  • B. Mackness et al.

    The paraoxonase gene family and coronary heart disease

    Curr Opin Lipidol

    (2002)
  • C.E. Furlong et al.

    Pharmacogenomic considerations of the paraoxonase polymorphisms

    Pharmacogenomics

    (2002)
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    The authors have no conflicts of interest to disclose.

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