title: Importance of junctional adhesion molecule-A for neointimal lesion formation and infiltration in atherosclerosis-prone mice.
abstract: OBJECTIVE
  Although junctional adhesion molecule-A (JAM-A) has recently been implicated in leukocyte recruitment on early atherosclerotic endothelium and after reperfusion injury, its role in neointima formation after arterial injury remains to be elucidated.
  
  
  RESULTS
  Here we show that the genetic deletion of JAM-A in apolipoprotein E-deficient (apoE(-/-)) mice significantly reduced neointimal hyperplasia after wire injury of carotid arteries without altering medial area. This was associated with a significant decrease in neointimal macrophage content, whereas the relative content of smooth muscle cells and endothelial recovery was unaltered in JAM-A(-/-)apoE(-/-) compared with JAM-A(+/+)apoE(-/-) lesions. In carotid arteries perfused ex vivo, deficiency in JAM-A significantly impaired the recruitment of monocytes 1 week, but not 1 day, after injury. These effects were paralleled by an attenuation of monocyte arrest and transmigration on activated JAM-A(-/-)apoE(-/-) versus JAM-A(+/+)apoE(-/-) endothelial cells under flow conditions in vitro. A mechanism underlying reduced recruitment was implied by findings that the luminal expression of the arrest chemokine RANTES in injured arteries and its endothelial deposition by activated platelets in vitro were diminished by JAM-A deficiency.
  
  
  CONCLUSIONS
  Our data provide the first evidence to our knowledge for a crucial role of JAM-A in accelerated lesion formation and monocyte infiltration in atherosclerosis-prone mice.
authors.affiliation: Department of Molecular Cardiovascular Research, RWTH University Hospital, Aachen, Germany.
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Line
authors.initials: L
authors.lastname: Fraemohs
authors.forename: Philipp
authors.initials: P
authors.lastname: von Hundelshausen
authors.forename: Rory R
authors.initials: RR
authors.lastname: Koenen
authors.forename: Monica
authors.initials: M
authors.lastname: Corada
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology; D002340:Carotid Artery Diseases / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006965:Hyperplasia; D062726:Junctional Adhesion Molecules; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D062726:Junctional Adhesion Molecules