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
Liang JingWei Wang

Abstract

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. 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. 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 e...Continue Reading

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Citations

Sep 25, 2018·Chinese Medical Journal·Ling-Bing MengTao Gong
Apr 25, 2017·Vascular·Zhengze Dai, Gelin Xu

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Methods Mentioned

BETA
Flow Cytometric
flow cytometry
electrophoresis
X-ray
SMA
Infection
FACS

Software Mentioned

ImageJ2x

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