Macrophage gene expression and foam cell formation are regulated by plasminogen.
نویسندگان
چکیده
BACKGROUND Deciphering the molecular and cellular processes that govern macrophage foam cell formation is critical to understanding the basic mechanisms underlying atherosclerosis and other vascular pathologies. METHODS AND RESULTS Here, we identify a pivotal role of plasminogen (Plg) in regulating foam cell formation. Deficiency of Plg inhibited macrophage cholesterol accumulation on exposure to hyperlipidemic conditions in vitro, ex vivo, and in vivo. Gene expression analysis identified CD36 as a regulated target of Plg, and macrophages from Plg(-/-) mice had decreased CD36 expression and diminished foam cell formation. The Plg-dependent CD36 expression and foam cell formation depended on conversion of Plg to plasmin, binding to the macrophage surface, and the consequent intracellular signaling that leads to production of leukotriene B4. Leukotriene B4 rescued the suppression of CD36 expression and foam cell formation arising from Plg deficiency. CONCLUSIONS Our findings demonstrate an unanticipated role of Plg in the regulation of gene expression and cholesterol metabolism by macrophages and identify Plg-mediated regulation of leukotriene B4 as an underlying mechanism.
منابع مشابه
Macrophage Gene Expression and Foam Cell Formation is Regulated by Plasminogen Running title :
Re Re Rese e ear ar rc ch ch I I Ins ns nst ti titu tu tute te te, Ca Ca Case se e W W Weste t t r r rn R Res s serv v ve e Un Un Univ iv iver ersi s s ty Ad Add dress f for C Correspo d ndence: Abstract: Background—Deciphering the molecular and cellular processes that govern macrophage foam
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ورودعنوان ژورنال:
- Circulation
دوره 127 11 شماره
صفحات -
تاریخ انتشار 2013