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lüll Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling Redmond EM; Liu W; Hamm K; Hatch E; Cahill PA; Morrow DPLoS One 2014[]; 9 (1): e84122OBJECTIVES: To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling. METHODS AND 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. CONCLUSION: These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.|*Gene Transfer Techniques[MESH]|Animals[MESH]|Carotid Arteries/metabolism/pathology/physiopathology[MESH]|Carotid Artery Injuries/*pathology/*physiopathology[MESH]|Cell Proliferation[MESH]|Male[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Myocytes, Smooth Muscle/metabolism/pathology[MESH]|RNA, Small Interfering/*administration & dosage/metabolism[MESH]|Receptor, Notch1/*genetics/*metabolism[MESH]|Signal Transduction[MESH] |