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

Article

关键词: MIGRATION-INHIBITORY FACTOR;    ENDOTHELIAL-CELLS;    EXPRESSION;    COMPLEMENT;    LIPOPOLYSACCHARIDE;    ADHESION;    LESIONS;    LDL;    ATHEROGENESIS;    DEFICIENT;   

DOI  :  10.1161/hc3401.093153

来源: SCIE

【 摘 要 】

Background-On the basis of our concept that atherosclerosis has an immunopathological background, we tested whether activation of the innate immune system influences its progression. Methods and Results-Hypercholesterolemic (0.5% wt/wt diet) rabbits received either repeated intravenous injections of endotoxin (Escherichia coli lipopolysaccharide 1.25 to 2.5 mug, once per week) or a self-limiting cutaneous Staphylococcus aureus infection with or without a quinolone antibiotic. Measured laboratory parameters, including LDL Sta and HDL cholesterols, were similar in the different groups of hypercholesterolemic animals. All endotoxin-treated animals developed transient episodes of fever after endotoxin administration. The extent of atherosclerosis was evaluated by computer-assisted morphometry in the aortas en face (Sudan IV) and by histology at 8 weeks after start of the experiments. Endotoxin-treated animals exhibited significantly 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 atherosclerosis has an immunopathological component and render it improbable that a single infectious agent should assume particular importance in its initiation or progression.

【 授权许可】

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