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

Liang Jing; Wenlong Wang; Shuangshuang Zhang; Minjie Xie; Daishi Tian; Xiang Luo; Daowen Wang; Qin Ning; Jiagao Lü; Wei Wang

doi:10.1371/journal.pone.0118826

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

PLoS One. 2015 Mar 11;10(3):e0118826. doi: 10.1371/journal.pone.0118826. eCollection 2015.

Authors

Affiliations

¹ Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
² Department of Cardiovascular Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
³ Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

Abstract

Aims: 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.

Methods and 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.

Conclusion: 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / pharmacology
Balloon Occlusion
Carotid Arteries / pathology*
Cell Proliferation*
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis
Cyclin-Dependent Kinase Inhibitor p27 / genetics*
Endothelium, Vascular / physiopathology
G1 Phase Cell Cycle Checkpoints
Green Fluorescent Proteins / biosynthesis
Green Fluorescent Proteins / genetics
Lentivirus / genetics
Male
Microfilament Proteins / genetics*
Muscle Proteins / genetics*
Muscle, Smooth, Vascular / pathology
Myocytes, Smooth Muscle / physiology*
Neointima / metabolism
Paclitaxel / pharmacology
Rats, Wistar
Vascular Remodeling
Wound Healing

Substances

Antineoplastic Agents, Phytogenic
Microfilament Proteins
Muscle Proteins
enhanced green fluorescent protein
transgelin
Green Fluorescent Proteins
Cyclin-Dependent Kinase Inhibitor p27
Paclitaxel

Grants and funding

This work was supported by grants from Natural Science Foundation of China (81030021 to WW, 30870641 to LJ) and National Basic Research Program (2011CB504403 to WW) and Program for Changjiang Scholars and Innovative Research Team in University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.