title: Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.
abstract: OBJECTIVE
  To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling.
  
  
  RESULTS
  Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.
  
  
  CONCLUSIONS
  These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Redmond
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Katie
authors.initials: K
authors.lastname: Hamm
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Hatch
authors.affiliation: Vascular Health Research Centre, Dublin City University, Dublin, Ireland.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Cahill
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Morrow
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020212:Carotid Artery Injuries / Q000473:pathology* / Q000503:physiopathology*; D049109:Cell Proliferation; D018014:Gene Transfer Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D034741:RNA, Small Interfering; D051881:Receptor, Notch1