Preethi Mani1, Kiyoko Uno1, MyNgan Duong1, Kathy Wolski1, Steven Spalding1, M Elaine Husni1, Stephen J Nicholls1. 1. 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.
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.
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: Lin T Guey; Clive R Pullinger; Brian Y Ishida; Patricia M O'Connor; Christian Zellner; Omar L Francone; Jason M Laramie; Josefina M Naya-Vigne; Ketevan A Siradze; Prakash Deedwania; Rita F Redberg; Philip H Frost; Albert B Seymour; John P Kane; Mary J Malloy Journal: Am J Cardiol Date: 2011-08-01 Impact factor: 2.778
Authors: William E Boden; Jeffrey L Probstfield; Todd Anderson; Bernard R Chaitman; Patrice Desvignes-Nickens; Kent Koprowicz; Ruth McBride; Koon Teo; William Weintraub Journal: N Engl J Med Date: 2011-11-15 Impact factor: 91.245
Authors: Nisha I Parikh; Mariana Gerschenson; Kara Bennett; Louie Mar M Gangcuangco; Mary S Lopez; Nehal N Mehta; Martin P Playford; Beau K Nakamoto; Todd B Seto; Dominic C Chow; Cecilia M Shikuma Journal: Atherosclerosis Date: 2014-12-20 Impact factor: 5.162
Authors: Andrew J Murphy; Kevin J Woollard; Anh Hoang; Nigora Mukhamedova; Roslynn A Stirzaker; Sally P A McCormick; Alan T Remaley; Dmitri Sviridov; Jaye Chin-Dusting Journal: Arterioscler Thromb Vasc Biol Date: 2008-07-10 Impact factor: 8.311
Authors: Inmaculada Concepción Aranda-Valera; Iván Arias de la Rosa; Rosa Roldán-Molina; María Del Carmen Ábalos-Aguilera; Carmen Torres-Granados; Alejandra Patiño-Trives; María Luque-Tevar; Alejandro Ibáñez-Costa; Rocío Guzmán-Ruiz; María Del Mar Malagón; Alejandro Escudero-Contreras; Chary López-Pedrera; Eduardo Collantes-Estévez; Nuria Barbarroja Journal: Pediatr Rheumatol Online J Date: 2020-07-14 Impact factor: 3.054