title: Macrophage gene expression and foam cell formation are regulated by plasminogen.
abstract: 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.
  
  
  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.
authors: Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Riku
authors: R
authors: Das
authors: Swetha
authors: S
authors: Ganapathy
authors: Ganapati H
authors: GH
authors: Mahabeleshwar
authors: Carla
authors: C
authors: Drumm
authors: Maria
authors: M
authors: Febbraio
authors: Mukesh K
authors: MK
authors: Jain
authors: Edward F
authors: EF
authors: Plow
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010958:Plasminogen / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D007975:Leukotriene B4; D010958:Plasminogen; D002784:Cholesterol
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