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

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.

Keywords: vasculitis, atherosclerosis, paraoxonase, oxidized-LDL, inflammation

Abbreviations: Ab, antibodies, aCL, anticardiolipin antibodies, ANCA, antineutrophil cytoplasmic antibodies, Apo-AI, apolipoprotein A-I, APS, antiphospholipid syndrome, ASV, active systemic vasculitis, BHT, butylated hydroxytoluene, BSA, bovine serum albumin, CRP, C-reactive protein, CSS, Churg–Strauss syndrome, ELISA, enzyme-linked immunoabsorbent assay, ESRD, end-stage renal disease, GCA, giant-cell arteritis, HDL, high-density lipoproteins, HS, healthy subjects, HS-CRP, hypersensitive-CRP, HSP, Henoch–Schönlein purpura, LDL, low-density lipoprotein, LDL-IC, LDL-immune complexes, LV, leukocytoclastic vasculitis, MDA, malondialdehyde, MDA-LDL, highly oxidized LDL, MPA, microscopic polyangiitis, N-LDL, native LDL, OD, optical density, ox-LDL, oxidized-LDL, PBS, phosphate-buffered saline, PON1, paraoxonase 1, RSV, remission of systemic vasculitis, SLE, systemic lupus erythematosus, SV, systemic vasculitis, TA, Takayasu’s arteritis, WG, Wegener’s granulomatosis