Pro-inflammatory high-density lipoproteins and atherosclerosis are induced in lupus-prone mice by a high-fat diet and leptin.
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.
Hahn
B H
BH
Division of Rheumatology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA. bhahn@mednet.ucla.edu
Lourencço
E V
EV
McMahon
M
M
Skaggs
B
B
Le
E
E
Anderson
M
M
Iikuni
N
N
Lai
C K
CK
La Cava
A
A
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
D004041:Dietary Fats; D020738:Leptin; D008075:Lipoproteins, HDL
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