PMID- 26885490 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160217 LR - 20200930 IS - 2223-3652 (Print) IS - 2223-3660 (Electronic) IS - 2223-3652 (Linking) VI - 6 IP - 1 DP - 2016 Feb TI - HDL function and subclinical atherosclerosis in juvenile idiopathic arthritis. PG - 34-43 LID - 10.3978/j.issn.2223-3652.2015.12.14 [doi] AB - 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. FAU - Mani, Preethi AU - Mani P AD - 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. FAU - Uno, Kiyoko AU - Uno K AD - 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. FAU - Duong, MyNgan AU - Duong M AD - 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. FAU - Wolski, Kathy AU - Wolski K AD - 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. FAU - Spalding, Steven AU - Spalding S AD - 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. FAU - Husni, M Elaine AU - Husni ME AD - 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. FAU - Nicholls, Stephen J AU - Nicholls SJ AD - 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. LA - eng PT - Journal Article PL - China TA - Cardiovasc Diagn Ther JT - Cardiovascular diagnosis and therapy JID - 101601613 PMC - PMC4731577 OTO - NOTNLM OT - Arthritis OT - atherosclerosis OT - high-density lipoproteins (HDL) cholesterol OT - juvenile COIS- Conflicts of Interest: SJ Nicholls: Research Grant; Modest; Amgen, Inc., AstraZeneca Pharmaceuticals LP, Roche, Lilly USA, LLC, Resverlogix Corp, Novartis Pharmaceuticals Corporation. Consultant/Advisory Board; Modest; Takeda Pharmaceuticals North America, Inc, Roche, Merck & Co., Inc. The other authors have no conflicts of interest to declare. EDAT- 2016/02/18 06:00 MHDA- 2016/02/18 06:01 PMCR- 2016/02/01 CRDT- 2016/02/18 06:00 PHST- 2016/02/18 06:00 [entrez] PHST- 2016/02/18 06:00 [pubmed] PHST- 2016/02/18 06:01 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - cdt-06-01-034 [pii] AID - 10.3978/j.issn.2223-3652.2015.12.14 [doi] PST - ppublish SO - Cardiovasc Diagn Ther. 2016 Feb;6(1):34-43. doi: 10.3978/j.issn.2223-3652.2015.12.14.