Plasma from systemic lupus patients compromises cholesterol homeostasis: a potential mechanism linking autoimmunity to atherosclerotic cardiovascular disease.
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.
Reiss
Allison B
AB
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
Anwar
Kamran
K
Merrill
Joan T
JT
Chan
Edwin S L
ES
Awadallah
Nahel W
NW
Cronstein
Bruce N
BN
Michael Belmont
H
H
Belilos
Elise
E
Rosenblum
Gary
G
Belostocki
Kristina
K
Bonetti
Lois
L
Hasneen
Kowser
K
Carsons
Steven E
SE
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
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