PEG-Et Nanocarrier Mediated ShSmad3 Inhibits Restenosis

Intimal hyperplasia is a pathological process which contributes to several clinical problems such as atherosclerosis and postangioplasty restenosis.Vascular will conduct a kind of remodeling after injury thus resulting in intimal thickening,and vascular smooth muscle cells(VMSCs)play major role in this process,and current therapy which aims to antagonize restenosis of vascular is mainly inhibiting VSMCs proliferation.Studies found that inhibition of Smad3 expression can inhibit the proliferation of VSMCs and reduce the secretion collagen thus inhibiting intimal thickening,suggesting that inhibiting Smad3 expression is an effective strategy to prevent restenosis.In our previous study,we designed a novel cross-linked polyethylenimine(PEI)derivative,namely polyethylene glycol-graft-polyetylenimine derivative(PEG-Et 1:1).Results showed that PEG-Et 1:1 could condense Smad3 sh RNA(sh Smad3)into spherical and uniform nanoparticles,it ccould also delivery sh Smad3 to decrease the expression of Smad3 in VSMCs and inhibit VSMCs proliferation in vitro.On the basis of previous study,in this research we tried to apply PEG-Et 1:1 to deliver the sh Smad3 to local artery for preventing intimal thickening after vascular injury in vivo.Results showed that PEG-Et1:1-mediated delivery of sh Smad3 efficiently reduced Smad3 expression and inhibited intimal thickening after vascular injury,reduced VSMCs proliferation and diminished collagen content was also found in PEG-Et/sh Smad3 polyplex treated group.In addition,inhibition of Smad3 expression caused significant up-regulation of matrix metalloproteinases(MMP1,MMP2 and MMP9)expression and down-regulation of tissue inhibitor of metalloproteinase1(TIMP1)expression.To sum up,PEG-Et1:1-mediated delivery of sh Smad3 is a feasible strategy to prevent intimal thickening.