title: Vein graft arterialization causes differential activation of mitogen-activated protein kinases.
abstract: OBJECTIVE
  Vascular injury results in activation of the mitogen-activated protein kinases-extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38(MAPK)-which have been implicated in cell proliferation, migration, and apoptosis. The goal of this study was to characterize mitogen-activated protein kinase activation in arterialized vein grafts.
  
  
  METHODS
  Carotid artery bypass using reversed external jugular vein was performed in 29 dogs. Vein grafts were harvested after 30 minutes and 3, 8, and 24 hours, and 4, 7, 14, and 28 days. Contralateral external jugular vein and external jugular vein interposition vein-to-vein grafts were used as controls. Vein graft extracts were analyzed for extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38(MAPK) activation. Proliferating cell nuclear antigen expression was investigated as a parameter of cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining and intimal hyperplasia by morphometric examination of tissue sections.
  
  
  RESULTS
  Significant intimal hyperplasia was observed at 28 days. Over the time points studied, vein graft arterialization resulted in bimodal activation of both extracellular-signal regulated kinase and p38(MAPK) (30 minutes through 3 hours; 4 days) but did not induce activation of c-jun N-terminal kinase. Proliferating cell nuclear antigen expression increased from days 1 through 28, and apoptosis increased between 8 and 24 hours.
  
  
  CONCLUSIONS
  Vein graft arterialization induces bimodal activation of extracellular-signal regulated kinase and p38(MAPK); however, in contrast with what is described in arterial injury, it does not induce c-jun N-terminal kinase activation. These results provide the first comprehensive characterization of the mitogen-activated protein kinase signaling pathways activated in vein graft arterialization and identify mitogen-activated protein kinases as potential mediators of vein graft remodeling and subsequent intimal hyperplasia.
authors.affiliation: Seymour Cohn Cardiovascular Research Laboratory, Division of Cardiothoracic Surgery, Department of Surgery, New York University School of Medicine, New York 10016, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Saunders
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pintucci
authors.forename: Costas S
authors.initials: CS
authors.lastname: Bizekis
authors.forename: Ram
authors.initials: R
authors.lastname: Sharony
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Hyman
authors.forename: Fiorella
authors.initials: F
authors.lastname: Saponara
authors.forename: F Gregory
authors.initials: FG
authors.lastname: Baumann
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Grossi
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Colvin
authors.forename: Paolo
authors.initials: P
authors.lastname: Mignatti
authors.forename: Aubrey C
authors.initials: AC
authors.lastname: Galloway
mesh_terms: D000818:Animals; D017209:Apoptosis; D002339:Carotid Arteries / Q000601:surgery*; D002455:Cell Division; D004285:Dogs; D004789:Enzyme Activation; D006965:Hyperplasia; D048031:JNK Mitogen-Activated Protein Kinases; D007601:Jugular Veins / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D017539:Tunica Intima / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases