title: EMAP-II downregulation contributes to the beneficial effects of rapamycin after vascular injury.
abstract: OBJECTIVE
  Neointima formation after vascular injury is strongly associated with inflammation. Rapamycin inhibits human neointima formation and reduces expression of the proinflammatory cytokine endothelial-monocyte activating peptide II (EMAP-II) in vitro. Here we investigated the interplay between EMAP-II and rapamycin after vascular injury in vivo.
  
  
  RESULTS
  In a mouse model of vascular injury, mice were either not treated, given everolimus, a rapamycin derivate, or subjected to simultaneous challenge with everolimus and EMAP-II. EMAP-II expression was measured in coronary artery smooth muscle cells (CASMC) and monocytic cells in vitro and in patients after percutaneous coronary intervention (PCI). After vascular injury, rapamycin reduced neointima formation and adventitial thickening. Immunohistochemistry revealed reduced EMAP-II protein expression and suppressed recruitment of inflammatory cells. Simultaneous challenge with EMAP-II counteracted these effects of rapamycin. Expression of EMAP-II and its inhibition by rapamycin was confirmed in CASMC and monocytic cells. In patients, EMAP-II upregulation was confined to PCI of distal coronary artery segments and profoundly suppressed by oral rapamycin treatment.
  
  
  CONCLUSIONS
  These data suggest important yet unrecognized roles of EMAP-II and adventitial inflammation in neointima formation: Through inhibition of EMAP-II, rapamycin reduces the recruitment of inflammatory cells to the adventitia and supports an early and bland healing.
authors.affiliation: Klinik für Herz- und Kreislaufkrankheiten, I. Medizinische Klinik und Deutsches Herzzentrum der Technischen Universität München, Lazarettstr. 36, D-80636 München, Germany.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Nührenberg
authors.forename: Nicolas
authors.initials: N
authors.lastname: Langwieser
authors.forename: Johannes B K
authors.initials: JB
authors.lastname: Schwarz
authors.forename: Yonghao
authors.initials: Y
authors.lastname: Hou
authors.forename: Pamela
authors.initials: P
authors.lastname: Frank
authors.forename: Falko
authors.initials: F
authors.lastname: Sorge
authors.forename: Susanne
authors.initials: S
authors.lastname: Matschurat
authors.forename: Stefan
authors.initials: S
authors.lastname: Seidl
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.forename: Albert
authors.initials: A
authors.lastname: Schömig
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Clauss
authors.forename: Dietlind
authors.initials: D
authors.lastname: Zohlnhöfer
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000517:prevention & control; D003331:Coronary Vessels / Q000473:pathology; D016207:Cytokines / Q000502:physiology*; D015536:Down-Regulation; D007249:Inflammation / Q000209:etiology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology*; D020123:Sirolimus / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D020123:Sirolimus