title: Pro-inflammatory high-density lipoproteins and atherosclerosis are induced in lupus-prone mice by a high-fat diet and leptin.
abstract: Atherosclerosis is accelerated in people with systemic lupus erythematosus, and the presence of dysfunctional, pro-inflammatory high-density lipoproteins is a marker of increased risk. We developed a mouse model of multigenic lupus exposed to environmental factors known to accelerate atherosclerosis in humans - high-fat diet with or without injections of the adipokine leptin. BWF1 mice were the lupus-prone model; BALB/c were non-autoimmune controls. High-fat diet increased total serum cholesterol in both strains. In BALB/c mice, non-high-density lipoprotein cholesterol levels increased; they did not develop atherosclerosis. In contrast, BWF1 mice on high-fat diets developed increased quantities of high-density lipoproteins as well as elevated high-density lipoprotein scores, indicating pro-inflammatory high-density lipoproteins; they also developed atherosclerosis. In the lupus-prone strain, addition of leptin increased pro-inflammatory high-density lipoprotein scores and atherosclerosis, and accelerated proteinuria. These data suggest that environmental factors associated with obesity and metabolic syndrome can accelerate atherosclerosis and disease in a lupus-prone background.
authors.affiliation: Division of Rheumatology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA. bhahn@mednet.ucla.edu
authors.forename: B H
authors.initials: BH
authors.lastname: Hahn
authors.forename: E V
authors.initials: EV
authors.lastname: Lourencço
authors.forename: M
authors.initials: M
authors.lastname: McMahon
authors.forename: B
authors.initials: B
authors.lastname: Skaggs
authors.forename: E
authors.initials: E
authors.lastname: Le
authors.forename: M
authors.initials: M
authors.lastname: Anderson
authors.forename: N
authors.initials: N
authors.lastname: Iikuni
authors.forename: C K
authors.initials: CK
authors.lastname: Lai
authors.forename: A
authors.initials: A
authors.lastname: La Cava
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004032:Diet; D004041:Dietary Fats / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020738:Leptin / Q000276:immunology*; D008075:Lipoproteins, HDL / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D024821:Metabolic Syndrome / Q000150:complications; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D009765:Obesity / Q000150:complications; D012307:Risk Factors
chemical_list: D004041:Dietary Fats; D020738:Leptin; D008075:Lipoproteins, HDL
references.citation: Kidney Int. 1999 Sep;56(3):860-72
references.pmid: 10469355
references.citation: Am J Pathol. 2004 Feb;164(2):385-90
references.pmid: 14742244
references.citation: Metabolism. 2007 Nov;56(11):1542-9
references.pmid: 17950106
references.citation: Nat Rev Immunol. 2004 May;4(5):371-9
references.pmid: 15122202
references.citation: Arterioscler Thromb Vasc Biol. 2000 Aug;20(8):1946-52
references.pmid: 10938016
references.citation: Life Sci. 2006 Apr 18;78(21):2523-32
references.pmid: 16438990
references.citation: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7018-23
references.pmid: 16636270
references.citation: Atherosclerosis. 2003 Sep;170(1):21-9
references.pmid: 12957679
references.citation: Arterioscler Thromb. 1993 Jun;13(6):932-43
references.pmid: 8499414
references.citation: Arthritis Rheum. 2006 Aug;54(8):2541-9
references.pmid: 16868975
references.citation: Arthritis Rheum. 2009 Aug;60(8):2428-37
references.pmid: 19644959
references.citation: Clin Immunol. 2008 May;127(2):168-75
references.pmid: 18325838
references.citation: Atherosclerosis. 2006 Nov;189(1):47-60
references.pmid: 16580676
references.citation: J Rheumatol. 2009 Feb;36(2):295-7
references.pmid: 19132788
references.citation: J Lipid Res. 2007 Apr;48(4):794-805
references.pmid: 17259598