title: Rapamycin limits the growth of established experimental abdominal aortic aneurysms.
abstract: OBJECTIVE
  Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease affecting 4-8% of men older than 60 years. No pharmacologic strategies limit disease progression, aneurysm rupture, or aneurysm-related death. We examined the ability of rapamycin to limit the progression of established experimental AAAs.
  
  
  METHODS
  AAAs were created in 10-12-week-old male C57BL/6J mice via the porcine pancreatic elastase (PPE) infusion method. Beginning 4 days after PPE infusion, mice were treated with rapamycin (5 mg/kg/day) or an equal volume of vehicle for 10 days. AAA progression was monitored by serial ultrasound examination. Aortae were harvested for histological analyses at sacrifice.
  
  
  RESULTS
  Three days after PPE infusion, prior to vehicle or rapamycin treatment, aneurysms were enlarging at an equal rate between groups. In the rapamycin group, treatment reduced aortic enlargement by 38%, and 53% at 3 and 10 days, respectively. On histological analysis, medial elastin and smooth muscle cell populations were relatively preserved in the rapamycin group. Rapamycin treatment also reduced mural macrophage density and neoangiogenesis.
  
  
  CONCLUSIONS
  Rapamycin limits the progression of established experimental aneurysms, increasing the translational potential of mechanistic target of rapamycin-related AAA inhibition strategies.
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rouer
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Xu
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Xuan
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Fujimura
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Glover
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Furusho
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gerritsen
authors.affiliation: Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: rld@stanford.edu.
authors.forename: R L
authors.initials: RL
authors.lastname: Dalman
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D018450:Disease Progression; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*; D020123:Sirolimus / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: Abdominal aortic aneurysm; Angiogenesis; Macrophage; Rapamycin