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Research Paper

Antisense to Transforming Growth Factor-β1 Facilitates the Apoptosis of Macrophages in Rat Vein Grafts

Heaton N.S. · Wolff R.A. · Malinowski R.L. · Hullett D.A. · Hoch J.R.

Author affiliations

W.S. Middleton VA Hospital and the University of Wisconsin School of Medicine and Public Health, Madison, Wisc., USA

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J Vasc Res 2008;45:365–374

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: August 10, 2007
Accepted: December 04, 2007
Published online: March 20, 2008
Issue release date: August 2008

Number of Print Pages: 10
Number of Figures: 3
Number of Tables: 1

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: https://www.karger.com/JVR

Abstract

Background: The success of peripheral vein grafts is limited by intimal hyperplasia. Transforming growth factor (TGF)-β1 has effects on cell proliferation, apoptosis and extracellular matrix synthesis. We have previously observed positive changes in vessel healing with antisense to TGF-β1. Methods: Adenovirus was used to transduce rat femoral artery vein grafts with antisense to TGF-β1 (Ad-AST) or the sequence encoding the bioactive form of TGF-β1 (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-β1 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.

© 2008 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: August 10, 2007
Accepted: December 04, 2007
Published online: March 20, 2008
Issue release date: August 2008

Number of Print Pages: 10
Number of Figures: 3
Number of Tables: 1

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: https://www.karger.com/JVR


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