通过在普朗尼克F127中编码Pin1 shRNA的慢病毒载体的局部应用预防新生内膜增生

Title:Prevention of Neointimal Hyperplasia by Local Application of Lentiviral Vectors Encoding Pin1 shRNA in Pluronic F127

Volume: 15 Issue: 6

Author(s): Lei Lv, Yaxue Shi, Rundan Duan, Hui Xie, Jiwei Zhang, Wei Liang, Guanhua Xue, Lan Zhang and Xiaozhong Huang

Affiliation:

关键词: Pin1，血管平滑肌细胞，新生内膜增生，普朗尼克F127，慢病毒。

摘要: Inhibition of intimal hyperplasia plays an important role in preventing restenosis. Previously, we reported the provocative role of Pin1 in regulating vascular smooth muscle cell (VSMC) proliferation. Here we intended to identify whether locally delivered lentivirus-mediated siPin1 via pluronic F127 (PF127) could inhibit neointimal formation and further explore the potential mechanisms thereof. In vitro studies revealed that lentivirus-mediated siPin1 dispersed in PF127 suppressed proliferation and induced senescence in VSMCs. Reduction of Pin1 expression resulted in a decrease of phospho-Akt (p-Akt) expression level in VSMCs. Reactivation of Akt phosphorylation overcame the siPin1-mediated senescence. In a rat wire injury model, periadventitial delivery of lentivirus-mediated siPin1 via PF127 produced inhibition of intimal hyperplasia 14 days after injury without evidence for toxicity. Furthermore, the reduction of intimal thickness was associated with a decreased amount of PCNA positive cells, decreased telomerase activity and shortened telomere length. Therefore, these results suggest that PF127 delivery of lentivirus-mediated siPin1 to artery may have a therapeutic potential for the treatment of restenosis.

Cite this article as:

Lei Lv, Yaxue Shi, Rundan Duan, Hui Xie, Jiwei Zhang, Wei Liang, Guanhua Xue, Lan Zhang and Xiaozhong Huang , Prevention of Neointimal Hyperplasia by Local Application of Lentiviral Vectors Encoding Pin1 shRNA in Pluronic F127, Current Gene Therapy 2015; 15 (6) . https://dx.doi.org/10.2174/1566523215666151013140859