Intraperitoneal administration of anti-c-fms monoclonal antibody prevents initial events of atherogenesis but does not reduce the size of advanced lesions in apolipoprotein E-deficient mice

Article; Proceedings Paper

关键词: COLONY-STIMULATING FACTOR;    GENE-EXPRESSION;    ATHEROSCLEROTIC LESIONS;    MESSENGER-RNA;    MACROPHAGE;    MOUSE;    CELLS;    HYPERCHOLESTEROLEMIA;    OSTEOPETROSIS;    INCREASES;   

DOI  :  10.1161/01.CIR.99.13.1740

来源: SCIE

【 摘 要 】

Background-Atherosclerosis results From complex inflammatory-fibroproliferative responses. To elucidate the central role of macrophage and macrophage-colony stimulating factor (M-CSF) during atherogenesis, we used a new strategy to administer to adult apolipoprotein E (apoE)-deficient mice a monoclonal antibody (AFS98) raised against c-fins, the receptor of M-CSF. Methods and Results-When 6-week-old apoE-deficient mice were fed a high-fat diet and injected with 2 mg of AFS98 intraperitoneally on alternate days for 6 weeks, accumulation of macrophage-derived foam cells in the aortic root was suppressed by 70% compared with that in controls. This preventive effect was associated with neither remarkable decrease of the number of circulating monocytes nor systemic growth retardation. In contrast, when apoE-deficient mice that had been fed a high-rat diet from 6 weeks of age were given AFS98 from 12 to 18 weeks of age, a minimal protective effect on lesion size was observed. Conclusions-These results suggest that (1) macrophage and M-CSF/c-fms pray an essential role in the arterial wall during development of the fatty streak lesion and (2) blockade of the M-CSF/c-fms pathway could act as protection From at least early atherogenesis but could have a less preventive effect on maintenance of the advanced lesions.

【 授权许可】

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