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Plasma from systemic lupus patients compromises cholesterol homeostasis: a potential mechanism linking autoimmunity to atherosclerotic cardiovascular disease

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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 µg 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.

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Acknowledgments

We thank Mr. Alexander Schoen for his technical assistance in manuscript design and assembly. This work was supported by an Innovative Research Grant from the Arthritis Foundation, National Center and by a grant from The National Institutes of Health/National Heart, Lung and Blood Institute HL073814 (Reiss). Additional support was provided by the Arthritis Foundation, New York Chapter and the Scleroderma Foundation (Chan), the National Institutes of Health (AR41911, AA13336 and GM56268), and the General Clinical Research Center (M01RR00096) (Cronstein).

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Correspondence to Allison B. Reiss.

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Reiss, A.B., Anwar, K., Merrill, J.T. et al. Plasma from systemic lupus patients compromises cholesterol homeostasis: a potential mechanism linking autoimmunity to atherosclerotic cardiovascular disease. Rheumatol Int 30, 591–598 (2010). https://doi.org/10.1007/s00296-009-1020-6

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  • DOI: https://doi.org/10.1007/s00296-009-1020-6

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