Accelerated atherosclerosis is independent of feeding high fat diet in systemic lupus erythematosus-susceptible LDLr-/- mice

N. A. Braun, N. S. Wade, E. K. Wakeland, Amy S. Major

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Individuals suffering from systemic lupus erythematosus (SLE) are predisposed to accelerate cardiovascular disease. Our laboratory has recently developed an animal model of SLE-accelerated atherosclerosis. We have shown that, following 8 weeks feeding high fat Western diet, radiation chimeras consisting of SLE-derived haematopoietic cells transferred to low-density lipoprotein (LDL)r-/- mice (LDLr.Sle) have increased atherosclerosis compared with C57Bl/6 bone marrow recipients (LDLr.B6). However, this feeding regimen resulted in significant mortality in SLE-susceptible mice compared with controls with surviving animals having extremely elevated serum cholesterol (>500 mg/dL) and increased serum markers of kidney pathology. To test the hypothesis that SLE-associated autoimmune dysregulation can exacerbate atherosclerosis under more mild serum cholesterol conditions (approximately 200 mg/dL), we examined SLE and lesion development in radiation chimeras fed either a normal chow or high fat Western diet for 8 weeks. High fat fed LDLr.Sle mice exhibited increased mortality and were significantly more hypertensive. LDLr.Sle mice had greater titres of antibodies against dsDNA, oxLDL and phospholipid compared with controls. Lupus-susceptibility increased the atherosclerotic lesions and the percentage of CD4+ T cells in the lesions of proximal aortas, independent of diet. These data show that increased dyslipidemia resulting from high-fat feeding can exacerbate autoimmunity and associated vascular complications. Conversely, they also show that autoimmune dysregulation can accelerate atherosclerosis in LDLr-deficient animals independent of feeding high fat diet. Collectively this study provides additional evidence that the accelerated atherosclerosis observed in SLE is autoimmune associated.

Original languageEnglish (US)
Pages (from-to)1070-1078
Number of pages9
JournalLupus
Volume17
Issue number12
DOIs
StatePublished - Dec 1 2008

Keywords

  • Atherosclerosis
  • Autoimmunity
  • High fat diet
  • Lupus

ASJC Scopus subject areas

  • Rheumatology

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