title: Macrophage apoptosis exerts divergent effects on atherogenesis as a function of lesion stage.
abstract: BACKGROUND
  Because apoptotic cell clearance appears to be defective in advanced compared with early atherosclerotic plaques, macrophage apoptosis may differentially affect plaque progression as a function of lesion stage.
  
  
  RESULTS
  We first evaluated the impact of targeted protection of macrophages against apoptosis at both early and advanced stages of atherosclerosis. Increased resistance of macrophages to apoptosis in early atherosclerotic lesions was associated with increased plaque burden; in contrast, it afforded protection against progression to advanced lesions. Conversely, sustained induction of apoptosis in lesional macrophages of advanced lesions resulted in a significant increase in lesion size. Such enhanced lesion size occurred as a result not only of apoptotic cell accumulation but also of elevated chemokine expression and subsequent intimal recruitment of circulating monocytes.
  
  
  CONCLUSIONS
  Considered together, our data suggest that macrophage apoptosis is atheroprotective in fatty streak lesions, but in contrast, defective clearance of apoptotic debris in advanced lesions favors arterial wall inflammation and enhanced recruitment of monocytes, leading to enhanced atherogenesis.
authors.affiliation: INSERM U939, Hôpital de Pitié, Paris, France.
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Gautier
authors.forename: Thierry
authors.initials: T
authors.lastname: Huby
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Betty
authors.initials: B
authors.lastname: Ouzilleau
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Miller
authors.forename: Flora
authors.initials: F
authors.lastname: Saint-Charles
authors.forename: Pierre
authors.initials: P
authors.lastname: Aucouturier
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis / Q000276:immunology*; D001158:Arteries / Q000276:immunology / Q000473:pathology; D001167:Arteritis / Q000276:immunology* / Q000473:pathology*; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000473:pathology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; D001323:Autoantibodies; D000939:Epitopes; D010743:Phospholipids; C505409:Casp3 protein, mouse; D053148:Caspase 3