Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.
Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.
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DOI：
10.1371/journal.pone.0084122
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Morrow D
中科院分区：
文献类型：
--
作者：
Redmond EM;Liu W;Hamm K;Hatch E;Cahill PA;Morrow D
确定Notch 1 siRNA血管周围递送在预防损伤诱导的动脉重塑中的功效。进行颈动脉结扎以诱导动脉重构。14天后，形态测定分析证实vSMC生长增加，随后中膜增厚和新生内膜形成。激光捕获显微切割、定量qRT-PCR和免疫印迹分析显示损伤血管中Notch 1受体和notch靶基因、Hrt 1和2表达显著增加。与混杂的siRNA对照相比，通过pluronic凝胶的Notch 1 siRNA的血管周围递送抑制了损伤诱导的Notch 1受体和靶基因表达的增加，同时将中膜增厚和新生内膜形成减少到损伤前的假手术水平。选择性Notch 1敲除还逆转了损伤诱导的促凋亡Bax表达的抑制，同时将损伤诱导的抗凋亡Bcl-XL表达降低至假手术对照水平。在平行实验中，增殖性细胞周期蛋白水平，通过PCNA表达测量，逆转到假手术后选择性Notch 1敲低的控制水平。这些结果表明，损伤诱导的动脉重塑可以通过局部血管周围递送Notch 1 siRNA成功地抑制。
To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling. 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. These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.
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影响因子：
0.2
作者：
Leng Q;Woodle MC;Lu PY;Mixson AJ
通讯作者：
Mixson AJ
DOI：
10.1161/atvbaha.110.215681
发表时间：
2010-12
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Morrow D;Cullen JP;Liu W;Cahill PA;Redmond EM
通讯作者：
Redmond EM
影响因子：
4.8
作者：
Sweeney, C;Morrow, D;Cahill, PA
通讯作者：
Cahill, PA
DOI：
10.1161/atvbaha.109.186890
发表时间：
2009-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Morrow D;Cullen JP;Liu W;Guha S;Sweeney C;Birney YA;Collins N;Walls D;Redmond EM;Cahill PA
通讯作者：
Cahill PA
影响因子：
10.5
作者：
Domenga, V;Fardoux, P;Joutel, A
通讯作者：
Joutel, A