Thorac Cardiovasc Surg 2006; 54(6): 388-392
DOI: 10.1055/s-2006-924410
Basic Science

© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of Carotis Venous Bypass Graft Disease by Intraoperative Nucleic Acid-Based Therapy in Rabbits

B. Kusch1 , S. Waldhans1 , A. Sattler2 , A. Wagner3 , M. Hecker3 , R. Moosdorf1 , S. Vogt1
  • 1Clinic for Cardiac Surgery, University Hospital Gießen and Marburg, Position Marburg, Marburg, Germany
  • 2Clinic for Cardiology, University Hospital Gießen and Marburg, Position Marburg, Marburg, Germany
  • 3Department of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany
Further Information

Publication History

Received January 18, 2006

Publication Date:
07 September 2006 (online)

Abstract

Background: Bypass graft stenosis after venous revascularisation procedures is characterised by massive neointimal and vascular smooth muscle cell proliferation triggered via endothelin-1 synthesis in the vessel wall. Decoy oligodesoxynucleotides (ODN) against the transcription factor activator protein-1 (AP-1) inhibits pre-pro-endothelin-1 expression. Methods: In 20 rabbits, an end-to-side jugular vein bypass to the carotid artery was performed: (group A) 8 grafts were treated with consensus AP-1 decoy ODN, (group B) 8 with mutated control ODN and (group C) 4 received no treatment. Explantation, histomorphometric and immunohistochemical evaluation was performed after 28 days. Results: Median intimal thickness of groups: (A) 28.3 µm, (B) 48.4 µm, (C) 71.1 µm. The decoy ODN-treated group showed a significant reduction of neointima formation (p = 0.029) and a downregulation of the endothelin receptor. Conclusions: In this model, neointima formation was reduced by local transfection with consensus decoy ODN against AP-1. Endothelin A and B receptor expression is downregulated. Molecular target nucleic acid-based therapies seem to be a future means of overcoming neointima proliferation in pressure-induced venous graft failure. Intraoperative local application makes it easy to use in routine revascularisation procedures.

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Prof. Sebastian Vogt

University Hospital Gießen and Marburg
Position Marburg
Cardiac Surgery

Baldingerstraße

35043 Marburg

Germany

Phone: + 49 6 42 12 86 62 23

Fax: + 49 6 42 12 86 89 52

Email: vogts@mailer.uni-marburg.de