title: HDL function and subclinical atherosclerosis in juvenile idiopathic arthritis.
abstract: BACKGROUND
  Increasing evidence suggests that inflammation adversely impacts the protective properties of high-density lipoproteins (HDL) and progression of atherosclerosis. The impact of early chronic inflammatory conditions on HDL function and vascular risk has not been well investigated.
  
  
  METHODS
  We compared measures of HDL particle distribution and functionality, in addition to measures of carotid intima-medial thickness (cIMT) in patients with juvenile idiopathic arthritis (JIA) and age matched controls.
  
  
  RESULTS
  JIA patients demonstrated lower levels of HDL cholesterol [47.0 (40.0, 56.0) vs. 56.0 (53.0, 61.0) mg/dL, P=0.04], total HDL [29.5 (27.9, 32.3) vs. 32.9 (31.6, 36.3) mg/dL, P=0.05] and large HDL [5.1 (3.7, 7.3) vs. 8.0 (6.7, 9.7) mg/dL, P=0.04] particles. In association JIA patients demonstrated greater cholesterol efflux mediated via ATP binding cassette A1 (ABCA1) [17.3% (12.8, 19.7) vs. 10.0% (5.8, 16.0), P=0.05] and less efflux mediated via ATP binding cassette G-1 (ABCG1) [3.2% (2.0, 3.9) vs. 4.8% (3.5, 5.8), P=0.01] and SR-B1 [6.9% (6.0, 8.4) vs. 9.1% (8.6, 10.2), P=0.002] compared with controls. Exposure of macrophages to serum from JIA patients resulted in a smaller increase in mRNA expression of ABCA1 (2.0±0.95 vs. 7.1±5.7 fold increase, P=0.01) and greater increases in expression of ABCG1 [1.4 (0.9, 1.5) vs. 0.8 (0.7, 1.1) fold increase, P=0.04] and SR-B1 (1.3±0.47 vs. 0.7±0.3 fold increase, P=0.001) compared with controls. Arylesterase (128.9±27.6 vs. 152.0±45.2 umoles/min/mL, P=0.04) activity and endothelial cell migration (491.2±68.9 vs. 634.2±227.4 cells/field, P=0.01) were less in JIA patients. No differences in cIMT were observed between JIA patients and controls.
  
  
  CONCLUSIONS
  The presence of JIA was associated with alterations in HDL particle distribution, cholesterol efflux and non-lipid transporting activities. The ultimate implication of these findings for cardiovascular risk requires further investigation.
authors.affiliation: 1 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA ; 2 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA ; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia ; 4 Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Preethi
authors.initials: P
authors.lastname: Mani
authors.affiliation: 1 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA ; 2 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA ; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia ; 4 Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Uno
authors.affiliation: 1 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA ; 2 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA ; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia ; 4 Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: MyNgan
authors.initials: M
authors.lastname: Duong
authors.affiliation: 1 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA ; 2 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA ; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia ; 4 Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Wolski
authors.affiliation: 1 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA ; 2 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA ; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia ; 4 Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Spalding
authors.affiliation: 1 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA ; 2 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA ; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia ; 4 Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: M Elaine
authors.initials: ME
authors.lastname: Husni
authors.affiliation: 1 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA ; 2 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA ; 3 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia ; 4 Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
keywords: Arthritis; atherosclerosis; high-density lipoproteins (HDL) cholesterol; juvenile