title: Prevention of Neointimal Hyperplasia by Local Application of Lentiviral Vectors Encoding Pin1 shRNA in Pluronic F127.
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.
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.forename: Yaxue
authors.initials: Y
authors.lastname: Shi
authors.forename: Rundan
authors.initials: R
authors.lastname: Duan
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Jiwei
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Guanhua
authors.initials: G
authors.lastname: Xue
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630, Dongfang Road, Shanghai, 200127, China. Huangxiaozhong@renji.com.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D023903:Coronary Restenosis / Q000517:prevention & control*; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries*; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D058426:Neointima / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019098:Telomerase / Q000378:metabolism; D059505:Telomere Homeostasis / Q000235:genetics; D014162:Transfection / Q000379:methods; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C414604:PDZD2 protein, rat; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase