Abstract 14913: Variable Effects on Lipid Transporting and Non-Lipid Transporting Functions of HDL in Young Patients With Chronic Inflammatory Arthritis
Background: Impaired high density lipoprotein (HDL) functionality may contribute to increased cardiovascular risk in adults with chronic inflammatory disorders. It has not been established if early changes in HDL function are present in young individuals with similar diseases.
Methods: Subjects with and without juvenile idiopathic arthritis (JIA) were compared. Apolipoprotein B depleted serum capacity to promote cholesterol efflux via ABCA-I (J774 macrophages), ABCG-I (baby hamster kidney cells) and SR-BI (Fu5AH hepatoma cells) was compared. Change in mRNA expression of ABCA-I, ABCG-I, and SR-BI on murine bone marrow-derived macrophages upon exposure to serum was also assessed. HDL particle distributions were characterized using NMR spectroscopy. Antioxidant activity by arylesterase and ability of serum to promote endothelial cell migration were compared.
Results: 29 patients with JIA and 14 healthy controls between the ages of 10-32 were studied. Patients were younger than controls (17.3±6.7 vs. 21.7±6.8 years, p= 0.05) and had lower HDL-C (47.0 (40.0, 56.0) vs. 56.0 (53.0, 63.0) mg/dL, p = 0.04). Patient serum demonstrated greater cholesterol efflux via ABCA-I (17.3 (12.8, 19.7) vs. 10.0 (5.8, 16.0)%, p=0.05), but less efflux via ABCG-I (3.2 (2.0, 3.9) vs. 4.8 (3.5, 5.8)%, p=0.01) and SR-BI (6.9 (6.0, 8.4) vs. 9.2 (8.6, 10.2)%, p=0.002). Exposure of macrophages to patient serum resulted in less expression of ABCA-I (2.0±0.9 vs. 7.1±5.7 fold increase, p=0.01), but greater expression of ABCG-I (1.37 (0.88, 1.52) vs. 0.76 (0.71, 1.07) fold increase, p=0.04) and SR-BI (1.3± 0.47 vs. 0.65±0.25 fold increase, p=0.001). Patients had less large HDL (5.1 (3.7, 7.3) vs. 8.0 (6.7, 9.7) mg/dL, p=0.04) and less HDL particles (29.5 (27.9, 32.3) vs. 32.9 (31.6, 36.3) particles, p=0.05). Arylesterase activity was lower in patients (128.9±27.6 vs. 152.0±45.2 umoles/min/mL, p = 0.04). Endothelial cell migration was lower upon exposure to patient serum (491.2±68.9 vs. 634.2±227.4 cells/field, p = 0.01).
Conclusions: Differential effects on HDL functionality are seen in young individuals with inflammatory arthritis, favoring lipid transport to smaller HDL particles. The potential impact of these changes on cardiovascular risk warrant further investigation.
- © 2013 by American Heart Association, Inc.