Context Accelerated atherosclerosis has been described in antiphospholipid syndrome, but the vascular abnormalities and the underlying mechanisms remain unclear.Objectives To compare vascular structure and function in patients with positive antiphospholipid antibodies (aPL) with controls and to assess their relationship with paraoxonase activity. Design, Setting, and ParticipantsA cross-sectional study of 77 women with positive antiphospholipid antibodies from a lupus outpatient clinic in London, England (90% of the eligible population) and 77 controls matched on frequency basis for age and cardiovascular risk factors between June 2006 and April 2009. Carotid intima media thickness (CIMT), flow-mediated dilatation, pulse wave velocity, and paraoxonase activity were measured in all patients. Anti-inflammatory and antioxidant properties of high-density lipoprotein (HDL) were examined.Main Outcome Measures CIMT, pulse wave velocity, flow-mediated dilatation, and paraoxonase. ResultsWomen with aPL had greater CIMT and pulse wave velocity compared with controls (mean [SD], 0.75 [0.16] vs 0.64 [0.

Objective. To determine whether antibodies against high-density lipoprotein (aHDL) and apolipoprotein A-I (aApo A-I) interfere with the anti-atherogenic functions of high-density lipoprotein (HDL) and relate to disease activity and damage in SLE. Methods. Seventy-seven SLE patients were compared with an age-and sex-frequency matched control group. Immunoglobulin G (IgG) aHDL, IgG aApoA-I, soluble vascular cell and intracellular cell adhesion molecules (VCAM-1 and ICAM-1, respectively) were measured by ELISA, paraoxonase (PON) activity by spectrophotometry, nitric oxide (NOx) metabolites by the Griess reaction, and total anti-oxidant capacity (TAC) by chemiluminescence. Results. Compared with controls, SLE patients showed higher titres of IgG aHDL (P < 0.0001) and IgG aApo A-I (P < 0.0001), lower PON activity (P < 0.0001), increased NOx (P < 0.

Patients with systemic lupus erythematosus (SLE) have an increased incidence of vascular disease, and oxidative stress is recognized as an important feature in this condition, despite the underlying mechanisms not being fully understood. In these patients, an interaction between lipoproteins and the immune system has been suggested, but most studies have only looked at antibodies against oxidized low-density lipoproteins. This study was undertaken to determine the presence of antibodies directed against high-density lipoproteins (HDL) and to identify a possible association between these antibodies and paraoxonase (PON), an antioxidant enzyme present in HDL. Plasma from 55 patients with SLE was collected and IgG aHDL and antiapolipoprotein A-I (aApo A-I) antibodies were assessed by enzyme-linked immunosorbent assay. Standardization of the method was performed in a control population of 150 healthy subjects. Plasma levels above 5 standard deviations of the mean of the control population were considered positive. PON activity was assessed by quantification of p-nitrophenol formation (micromol/mL/min). Patients with SLE had higher titers of aHDL (P < 0.0001) and aApo A-I (P < 0.0001) antibodies, and lower PON activity (P < 0.0001) than healthy controls. There was also a direct correlation between the titers of aHDL and aApo A-I antibodies (r = 0.61; P < 0.0001). PON activity was inversely correlated with aApo A-I (P = 0.0129) antibody levels. Anti-HDL and aApo A-I antibodies from patients with high titers were isolated and subsequently incubated with human HDL. These antibodies reduced PON activity up to a maximum of 70.2% and 78.4%, respectively. This study showed the presence of aHDL and aApo A-I antibodies in patients with SLE. These antibodies were associated with reduced PON activity in plasma, and the in vitro inhibition assay confirmed a direct inhibition of the enzyme activity.

We have previously demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A2B receptors. Here, we have tested the hypothesis that the control is exerted via an interaction between adenosine A2B and dopamine D2 receptors present in chemoreceptor cells. Experiments were performed in vitro in CB from 3 months rats. The effect of A2B adenosine and D2 dopamine agonists and antagonists applied alone or in combination were studied on basal (20%O2) and hypoxia (10%O2)‐evoked release of CA and cAMP content of CB. We have found that adenosine A2 agonists and D2 antagonists dose‐dependently increased basal and evoked release CA from the CB while A2 antagonists and D2 agonists had an inhibitory action. The existence of A2B‐D2 receptor interaction was established because the inhibitory action of A2 antagonists was abolished by D2 antagonists, and the stimulatory action of A2 agonists was abolished by D2 agonists. Further, A2 agonists increased and D2 agonist decreased cAMP content in the CB; their co‐application eliminated the response. The present results provide direct pharmacological evidence that an antagonistic interaction between A2B adenosine and D2 dopamine receptors exist in rat CB and would explain the dopamine‐adenosine interactions on ventilation previously observed.

Abnormalities of the lipid profile partly explain the atherogenic tendency of systemic lupus erythematosus but the picture is unclear in thrombotic primary antiphospholipid syndrome (PAPS). Herein we compare the lipid profile, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHO), apolipoprotein A (ApoA-I), apolipoprotein B (ApoB), triglycerides (TRY)), anti-lipoprotein antibodies, beta-2-glycoprotein I complexed to oxidized low-density lipoprotein (oxLDL-ss(2)GPI) and C-reactive protein (CRP) from thrombotic PAPS (n = 34), thrombotic patients with inherited thrombophilia (IT; n = 36), subjects persistently positive for antiphospholipid antibodies (aPL, n = 18) with no underlying autoimmune or non-autoimmune disorders and healthy controls (n = 28) and determined the reciprocal effects of anti-lipoprotein antibodies, the lipid profile, oxLDL-ss(2)GPI and CRP. Average concentrations of HDL (p < 0.0001), LDL (p < 0.0001), CHO (p = 0.0002), ApoA-I (p = 0.002) were lower in PAPS whereas average TRY was higher (p = 0.01) than other groups. Moreover, the aPL and PAPS group showed higher levels of IgG anti-HDL (p = 0.01) and IgG anti-ApoA-I (p < 0.0001) whereas the PAPS group showed greater average oxLDL-ss(2)GPI (p = 0.001) and CRP (p = 0.003). Within the PAPS group, IgG anti-HDL correlated negatively to HDL (p = 0.004) and was an independent predictor of oxLDL-ss2GPI (p = 0.009). HDL and ApoA-I correlated negatively with CRP (p = 0.001 and p = 0.007, respectively). IgG anti-HDL may hamper the antioxidant and anti-inflammatory effect of HDL favoring low-grade inflammation and enhanced oxidation in thrombotic PAPS.

PAPS is characterized by decreased NO(2)(-) in relation to type and number of vascular occlusions and to aPL titers. Nitrative stress and low grade inflammation are linked phenomena in PAPS and may have implications for thrombosis and atherosclerosis.

Low-grade inflammation and immune activation occur in thrombotic PAPS and relate to clinical features and aPL levels.

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