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

Rheumatol Int. 2010 Mar;30(5):591-8. doi: 10.1007/s00296-009-1020-6. Epub 2009 Jun 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Atherosclerosis / blood
  • Atherosclerosis / immunology*
  • Autoimmunity*
  • Case-Control Studies
  • Cells, Cultured
  • Cholestanetriol 26-Monooxygenase / genetics
  • Cholestanetriol 26-Monooxygenase / metabolism*
  • Cholesterol / metabolism*
  • Down-Regulation
  • Endothelial Cells / enzymology*
  • Endothelial Cells / immunology
  • Female
  • Foam Cells / enzymology
  • Gene Expression Regulation, Enzymologic
  • Homeostasis
  • Humans
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / immunology
  • Lipoproteins, LDL / metabolism
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / immunology
  • Monocytes / enzymology*
  • Monocytes / immunology
  • RNA, Messenger / metabolism
  • Receptors, Interferon / antagonists & inhibitors
  • Receptors, Interferon / immunology
  • Risk Factors
  • Young Adult

Substances

  • Lipoproteins, LDL
  • RNA, Messenger
  • Receptors, Interferon
  • acetyl-LDL
  • interferon gamma receptor
  • Interferon-gamma
  • Cholesterol
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase