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-fms, 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-fat 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 play 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.
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-fms, 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-fat 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 play 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.
Authors: Peter J Psaltis; Adriana Harbuzariu; Sinny Delacroix; Tyra A Witt; Eric W Holroyd; Daniel B Spoon; Scott J Hoffman; Shuchong Pan; Laurel S Kleppe; Cheryl S Mueske; Rajiv Gulati; Gurpreet S Sandhu; Robert D Simari Journal: Circulation Date: 2011-12-27 Impact factor: 29.690
Authors: Sina Tavakoli; John D Short; Kevin Downs; Huynh Nga Nguyen; Yanlai Lai; Wei Zhang; Paul Jerabek; Beth Goins; Mehran M Sadeghi; Reto Asmis Journal: Radiology Date: 2016-11-16 Impact factor: 11.105
Authors: James G Conway; Brad McDonald; Janet Parham; Barry Keith; David W Rusnak; Eva Shaw; Marilyn Jansen; Peiyuan Lin; Alan Payne; Renae M Crosby; Jennifer H Johnson; Lloyd Frick; Min-Hwa Jasmine Lin; Scott Depee; Sarva Tadepalli; Bart Votta; Ian James; Karen Fuller; Timothy J Chambers; Frederick C Kull; Stanley D Chamberlain; Jeff T Hutchins Journal: Proc Natl Acad Sci U S A Date: 2005-10-25 Impact factor: 11.205
Authors: Shungo Hiroyasu; Prameladevi Chinnasamy; Rong Hou; Kylie Hotchkiss; Isabel Casimiro; Xu-Ming Dai; E Richard Stanley; Nicholas E S Sibinga Journal: Arterioscler Thromb Vasc Biol Date: 2012-11-01 Impact factor: 8.311