title: Nanoparticle-mediated local delivery of an antisense TGF-β1 construct inhibits intimal hyperplasia in autogenous vein grafts in rats.
abstract: BACKGROUND
  Intimal hyperplasia is one of the most important causes of vascular graft failure. Numerous studies have correlated transforming growth factor-β1 (TGF-β1) with extracellular matrix (ECM) deposition, a hallmark of intimal thickening.
  
  
  RESULTS
  In the present study, we performed immunohistochemistry, RT-PCR, and Western blot to examine the dynamic expression of TGF-β1, TGF-β1 receptor type I (TGF-β 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 carotid artery. Additionally, we determined whether nanoparticle-mediated delivery of a TGF-β1 antisense-expressing construct prevented TGF-β1 expression and intimal hyperplasia in grafted veins. In grafted veins, the expression of TGF-β1 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-β 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-β1 antisense-expressing construct down-regulated TGF-β1 expression and inhibited intimal hyperplasia in grafted veins.
  
  
  CONCLUSIONS
  Our findings provide further evidence that TGF-β1 plays an integral role in the development of intimal hyperplasia after vascular injury. Nanoparticle-mediated delivery of a TGF-β1 antisense-expressing construct is a feasible strategy to target TGF-β1-induced intimal thickening.
authors.affiliation: Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China. daixw@sj-hospital.org
authors.forename: Da-Xin
authors.initials: DX
authors.lastname: Sun
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Tan
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Cui
authors.forename: Bao-Sheng
authors.initials: BS
authors.lastname: Wang
authors.forename: Xian-Wei
authors.initials: XW
authors.lastname: Dai
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006965:Hyperplasia / Q000378:metabolism / Q000517:prevention & control; D007601:Jugular Veins / Q000637:transplantation; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles; D058426:Neointima / Q000378:metabolism / Q000517:prevention & control*; D020320:Oligoribonucleotides, Antisense / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D014182:Transplantation, Autologous; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D058017:Vascular Grafting
chemical_list: D020320:Oligoribonucleotides, Antisense; D018125:Receptors, Transforming Growth Factor beta; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; C576840:MMP1 protein, rat; D020781:Matrix Metalloproteinase 1