title: Targeted inhibitory effect of Lenti-SM22alpha-p27-EGFP recombinant lentiviral vectors on proliferation of vascular smooth muscle cells without compromising re-endothelialization in a rat carotid artery balloon injury model.
abstract: OBJECTIVE
  In-stent restenosis remains a serious problem after the implantation of drug-eluting stents, which is attributable to neointima formation and re-endothelialization. Here, we tried to find a new method which aims at selectively inhibiting proliferation of vascular smooth muscle cells (VSMC) proliferation without inhibition of re-endothelialization.
  
  
  RESULTS
  We used the smooth muscle-specific SM22alpha promoter in a recombinant lentiviral vector to drive overexpression of cell-cycle inhibitor, p27, in VSMCs. p27 effectively inhibited VSMC proliferation mediated by cell cycle arrest at the G0/G1 checkpoint. The SM22alpha-p27 lentiviral vector inhibited VSMC proliferation more effectively than paclitaxel. Rats infected with Lenti-SM22alpha-p27 had a significantly lower intima/media (I/M) ratio and also showed inhibition of restenosis on day 28 after balloon injury. Moreover, the repair of injured endothelium, and re-endothelialization of the carotid artery wall, was not affected by the smooth muscle cell-specific expression of p27.
  
  
  CONCLUSIONS
  A recombinant lentiviral vector carrying the SM22alpha promoter was used to effectively infect and selectively overexpress p27 protein in VSMCs, leading to inhibition of intimal hyperplasia without compromising endothelial repair.
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Cardiovascular Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Daishi
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Cardiovascular Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Daowen
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Cardiovascular Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Jiagao
authors.initials: J
authors.lastname: Lü
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D021721:Balloon Occlusion; D002339:Carotid Arteries / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000503:physiopathology; D059585:G1 Phase Cell Cycle Checkpoints; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D058426:Neointima / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D017208:Rats, Wistar; D066253:Vascular Remodeling; D014945:Wound Healing
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008840:Microfilament Proteins; D009124:Muscle Proteins; C485184:enhanced green fluorescent protein; C051615:transgelin; D049452:Green Fluorescent Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017239:Paclitaxel