title: Plasma from systemic lupus patients compromises cholesterol homeostasis: a potential mechanism linking autoimmunity to atherosclerotic cardiovascular disease.
abstract: Atherosclerotic cardiovascular disease (ASCVD) contributes to morbidity and mortality in systemic lupus erythematosus (SLE). Immunologic derangements may disrupt cholesterol balance in vessel wall monocytes/macrophages and endothelium. We determined whether lupus plasma impacts expression of cholesterol 27-hydroxylase, an anti-atherogenic cholesterol-degrading enzyme that promotes cellular cholesterol efflux, in THP-1 human monocytes and primary human aortic endothelial cells (HAEC). THP-1 monocytes and HAEC were incubated in medium containing SLE patient plasma or apparently healthy control human plasma (CHP). SLE plasma decreased 27-hydroxylase message in THP-1 monocytes by 47 +/- 8% (p < 0.008) and in HAEC by 51 +/- 5.5% (n = 5, p < 0.001). THP-1 macrophages were incubated in 25% lupus plasma or CHP and cholesterol-loaded (50 microg ml(-1) acetylated low density lipoprotein). Lupus plasma more than doubled macrophage foam cell transformation (74 +/- 3% vs. 35 +/- 3% for CHP, n = 3, p < 0.001). Impaired cholesterol homeostasis in SLE provides further evidence of immune involvement in atherogenesis. Strategies to inhibit or reverse arterial cholesterol accumulation may benefit SLE patients.
authors: Department of Medicine, Vascular Biology Institute, Division of Rheumatology, Allergy and Immunology, Winthrop-University Hospital, 222 Station Plaza, North, Suite 502, Mineola, NY 11501, USA. AReiss@winthrop.org
authors: Allison B
authors: AB
authors: Reiss
authors: Kamran
authors: K
authors: Anwar
authors: Joan T
authors: JT
authors: Merrill
authors: Edwin S L
authors: ES
authors: Chan
authors: Nahel W
authors: NW
authors: Awadallah
authors: Bruce N
authors: BN
authors: Cronstein
authors: H
authors: H
authors: Michael Belmont
authors: Elise
authors: E
authors: Belilos
authors: Gary
authors: G
authors: Rosenblum
authors: Kristina
authors: K
authors: Belostocki
authors: Lois
authors: L
authors: Bonetti
authors: Kowser
authors: K
authors: Hasneen
authors: Steven E
authors: SE
authors: Carsons
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity; D016022:Case-Control Studies; D002478:Cells, Cultured; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000201:enzymology* / Q000276:immunology; D005260:Female; D005487:Foam Cells / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications / Q000276:immunology; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors / Q000276:immunology; D012307:Risk Factors; D055815:Young Adult; D000096743:Interferon gamma Receptor
chemical_list: D053493:Cholestanetriol 26-Monooxygenase; D002784:Cholesterol; D007371:Interferon-gamma; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C032629:acetyl-LDL; C506831:CYP27A1 protein, human