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

Publication ,  Journal Article
Heaton, NS; Wolff, RA; Malinowski, RL; Hullett, DA; Hoch, JR
Published in: J Vasc Res
2008

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.

Duke Scholars

Published In

J Vasc Res

DOI

EISSN

1423-0135

Publication Date

2008

Volume

45

Issue

5

Start / End Page

365 / 374

Location

Switzerland

Related Subject Headings

  • Veins
  • Transforming Growth Factor beta1
  • Transduction, Genetic
  • Time Factors
  • Rats, Inbred Lew
  • Rats
  • Proliferating Cell Nuclear Antigen
  • Oligonucleotides, Antisense
  • Male
  • Macrophages
 

Citation

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Heaton, N. S., Wolff, R. A., Malinowski, R. L., Hullett, D. A., & Hoch, J. R. (2008). Antisense to transforming growth factor-beta(1) facilitates the apoptosis of macrophages in rat vein grafts. J Vasc Res, 45(5), 365–374. https://doi.org/10.1159/000121406
Heaton, Nicholas S., Randal A. Wolff, Rita L. Malinowski, Debra A. Hullett, and John R. Hoch. “Antisense to transforming growth factor-beta(1) facilitates the apoptosis of macrophages in rat vein grafts.J Vasc Res 45, no. 5 (2008): 365–74. https://doi.org/10.1159/000121406.
Heaton NS, Wolff RA, Malinowski RL, Hullett DA, Hoch JR. Antisense to transforming growth factor-beta(1) facilitates the apoptosis of macrophages in rat vein grafts. J Vasc Res. 2008;45(5):365–74.
Heaton, Nicholas S., et al. “Antisense to transforming growth factor-beta(1) facilitates the apoptosis of macrophages in rat vein grafts.J Vasc Res, vol. 45, no. 5, 2008, pp. 365–74. Pubmed, doi:10.1159/000121406.
Heaton NS, Wolff RA, Malinowski RL, Hullett DA, Hoch JR. Antisense to transforming growth factor-beta(1) facilitates the apoptosis of macrophages in rat vein grafts. J Vasc Res. 2008;45(5):365–374.
Journal cover image

Published In

J Vasc Res

DOI

EISSN

1423-0135

Publication Date

2008

Volume

45

Issue

5

Start / End Page

365 / 374

Location

Switzerland

Related Subject Headings

  • Veins
  • Transforming Growth Factor beta1
  • Transduction, Genetic
  • Time Factors
  • Rats, Inbred Lew
  • Rats
  • Proliferating Cell Nuclear Antigen
  • Oligonucleotides, Antisense
  • Male
  • Macrophages