nanoparticle-mediated local delivery of an antisense tgf-β1 construct inhibits intimal hyperplasia in autogenous vein grafts in ratsnanoparticle-mediated当地交付一个反义tgf-β1构造抑制内膜的增生在大鼠自体静脉移植.pdfVIP

Nanoparticle-Mediated Local Delivery of an Antisense TGF-b 1 Construct Inhibits Intimal Hyperplasia in Autogenous Vein Grafts in Rats Da-Xin Sun*, Zhen Liu, Xiao-Dong Tan, Dong-Xu Cui, Bao-Sheng Wang, Xian-Wei Dai* Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China Abstract Background: Intimal hyperplasia is one of the most important causes of vascular graft failure. Numerous studies have correlated transforming growth factor-b1 (TGF-b1) with extracellular matrix (ECM) deposition, a hallmark of intimal thickening. Principal Findings: In the present study, we performed immunohistochemistry, RT-PCR, and Western blot to examine the dynamic expression of TGF-b1, TGF-b1 receptor type I (TGF-b RI), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) during intimal hyperplasia in grafted veins of a rat model generated by grafting a portion of the right internal jugular vein to the ipisiliary caroid artery. Additionally, we determined whether nanoparticle-mediated delivery of a TGF-b 1 antisense-expressing construct prevented TGF-b1 expression and intimal hyperplasia in grafted veins. In grafted veins, the expression of TGF-b1 significantly increased on day 3 after transplantation, peaked on day 7, slightly decreased on day 14, and returned to baseline levels on day 28. The positive expression of TGF-b RI in grafted veins remarkably increased on day 7, peaked on day 14, and decreased thereafter. MMP-1 expression decreased significantly, while TIMP-1 expression increased, significantly on days 14 and 28. Nanoparticle-mediated delivery of a TGF-b 1 antisense- expressing construct down-regulated TGF-b1 expression and inhibited intimal hyperplasia in grafted veins. Conclusions: O