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:Department of Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630, Dongfang Road, Shanghai, 200127, China.
Keywords:Pin1, Vascular smooth muscle cell, Neointimal hyperplasia, Pluronic F127, Lentivirus.
Abstract: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.
