Immunopathogenesis of atherosclerosis - Endotoxin accelerates atherosclerosis in rabbits on hypercholesterolemic diet

Citation
Ha. Lehr et al., Immunopathogenesis of atherosclerosis - Endotoxin accelerates atherosclerosis in rabbits on hypercholesterolemic diet, CIRCULATION, 104(8), 2001, pp. 914-920
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
104
Issue
8
Year of publication
2001
Pages
914 - 920
Database
ISI
SICI code
0009-7322(20010821)104:8<914:IOA-EA>2.0.ZU;2-R
Abstract
Background-On the basis of our concept that atherosclerosis has an immunopa thological background, we tested whether activation of the innate immune sy stem influences its progression. Methods and Results-Hypercholesterolemic (0.5% wt/wt diet) rabbits received either repeated intravenous injections of endotoxin (Escherichia coli lipo polysaccharide 1.25 to 2.5 mug, once per week) or a self-limiting cutaneous Staphylococcus aureus infection with or without a quinolone antibiotic. Me asured laboratory parameters, including LDL Sta and HDL cholesterols, were similar in the different groups of hypercholesterolemic animals. All endoto xin-treated animals developed transient episodes of fever after endotoxin a dministration. The extent of atherosclerosis was evaluated by computer-assi sted morphometry in the aortas en face (Sudan IV) and by histology at 8 wee ks after start of the experiments. Endotoxin-treated animals exhibited sign ificantly accelerated atherosclerosis compared with control animals (141 +/ - 38 versus 45 +/- 6 mm total lesion volume, n = 7 to 9 rabbits each, P < 0 .001). Conclusions-Nonspecific stimulation of the innate immune system accelerates cholesterol-induced atherosclerosis. These data support the concept that a therosclerosis has an immunopathological component and render it improbable that a single infectious agent should assume particular importance in its initiation or progression.