Abstract 4905: High Density Lipoprotein is Dysfunctional in Primary Antiphospholipid Syndrome and is Associated With Impaired Vascular Function

Abstract

Objectives: Antiphospholipid syndrome is characterised by increased thrombogenicity and/or pregnancy morbidity in the presence of raised levels of antiphospholipid antibodies (aPL). Increased oxidative properties of HDL (decreased activity of paraoxonase (PON) and accelerated atherosclerosis have been described in this syndrome. In this study, we assessed the functional properties of HDL and evaluated its impact on the vasculature in aPL positive patients and matched controls. Methods: We studied 77 women with positive aPL (APL) aged 46.6 ± 1.2 yrs (mean ± SE) and matched Controls of 77 women aged 47.5 ± 1.2 yrs. In all subjects, carotid intima media thickness (IMT), flow mediated dilatation (FMD) and pulse wave velocity (PWV) were measured. PON activity was assessed by measuring p-nitrophenol formation. HDL was isolated in APL (N = 6) and Controls (N = 6). The impact of HDL on human aortic endothelial cell (HAEC) nitric oxide (NO) and superoxide production were determined. Anti-inflammatory properties of HDL were examined by analyzing the effect of HDL on endothelial cell VCAM-1 expression and monocyte adhesion to activated HAEC. Results: APL had significantly increased IMT and PWV compared to Controls (0.75 ± 0.02mm vs 0.65 ± 0.01mm, p < 0.001 and 9.14 ± 0.18 m/s vs 8.56 ± 0.21m/s, p < 0.05 respectively) and decreased FMD (6.2 ± 0.5% vs 9.6 ± 0.5%, p < 0.001). PON activity was significantly reduced in APL compared to Controls (p = 0.006). PON activity was inversely associated with cIMT and PWV in APL (p < 0.05 for both) but not in Controls. HDL from Controls increased endothelial cell NO production, whereas in marked contrast HDL from APL reduced NO production by 20% (p < 0.0001). The beneficial effect of HDL on endothelial VCAM-1 expression, superoxide production and monocyte adhesion was diminished in APL (p < 0.05 for all). Conclusions: APL is associated with impaired vascular function and structure. PON activity is decreased in APL and is inversely associated with IMT and PWV. HDL in APL is associated with decreased endothelial NO production and has impaired anti-inflammatory and anti-oxidant properties. These findings suggest that HDL is dysfunctional in APL and support its role in promoting early vascular changes in antiphospholipid syndrome.