Antisense to transforming growth factor-beta(1) facilitates the apoptosis of macrophages in rat vein grafts.

Journal Article (Journal Article)

BACKGROUND: The success of peripheral vein grafts is limited by intimal hyperplasia. Transforming growth factor (TGF)-beta(1) has effects on cell proliferation, apoptosis and extracellular matrix synthesis. We have previously observed positive changes in vessel healing with antisense to TGF-beta(1). METHODS: Adenovirus was used to transduce rat femoral artery vein grafts with antisense to TGF-beta(1) (Ad-AST) or the sequence encoding the bioactive form of TGF-beta(1) (Ad-BAT). Grafts were harvested at 1, 2, 4 and 12 weeks and formalin fixed for immunohistochemical studies of the cell markers proliferating cellular nuclear antigen (proliferation) and active caspase 3 (apoptosis). In situ DNA fragmentation assays were also performed to confirm active caspase 3 results. RESULTS: Ad-AST treatment significantly (p = 0.05) increased apoptosis of macrophages inside the internal elastic lamina. In addition, Ad-AST treatment significantly increased the cellularity of the graft at early time points and reduced it at later time points (p = 0.01). CONCLUSION: The low levels of TGF-beta(1) in Ad-AST treatment promote apoptosis of macrophages and provide an environment that is more conducive to the proliferation or infiltration of cells that contribute to healthy vessels.

Full Text

Duke Authors

Cited Authors

  • Heaton, NS; Wolff, RA; Malinowski, RL; Hullett, DA; Hoch, JR

Published Date

  • 2008

Published In

Volume / Issue

  • 45 / 5

Start / End Page

  • 365 - 374

PubMed ID

  • 18354256

Electronic International Standard Serial Number (EISSN)

  • 1423-0135

Digital Object Identifier (DOI)

  • 10.1159/000121406


  • eng

Conference Location

  • Switzerland