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Reduction of vascular intimal-medial hyperplasia in polytetrafluoroethylene arteriovenous grafts via expression of an inhibitor of G protein signaling.

Publication ,  Journal Article
Fields, RC; Baig, K; Gaca, J; Milton, LG; Koch, WJ; Lawson, JH
Published in: Ann Vasc Surg
September 2005

Polytetrafluoroethylene (PTFE) arteriovenous (AV) grafts are performed routinely for vascular access. The limited life span of PTFE grafts is a major cause of morbidity. Graft failure is attributed to venous outflow tract vascular smooth muscle (VSM) hyperplasia, which is linked to heterotrimeric G protein signaling. We proposed that expression of a peptide inhibitor of G(betagamma) signaling (betaARKct) in the venous outflow of PTFE grafts would reduce hyperplasia and prolong graft patency. Left carotid to right external jugular vein PTFE AV grafts were placed in swine. The isolated external jugular vein was treated with an adenovirus encoding betaARKct, empty adenovirus, or phosphate-buffered saline for approximately 25 min. After 7 or 28 days, flow probe analysis was performed and the vein was harvested and analyzed for cross-sectional area comparison. After both 7 and 28 days, when compared to controls, treated animals demonstrated a statistically significant reduction in VSM hyperplasia with a reduction in cross-sectional intimal and medial areas of >40% (p < 0.05). Flow was maintained in treated grafts, while control groups demonstrated a >50% reduction (p < 0.05) at 7 days. Further, treated grafts demonstrated significant improvement in graft patency at 28 days (100% vs. 12% for treated and untreated grafts, respectively). The inhibition of G(betagamma) signaling reduces intimal-medial hyperplasia and prolongs graft patency in PTFE AV grafts. This represents a novel molecular therapeutic strategy for improving the patency of vascular access grafts.

Duke Scholars

Published In

Ann Vasc Surg

DOI

ISSN

0890-5096

Publication Date

September 2005

Volume

19

Issue

5

Start / End Page

712 / 718

Location

Netherlands

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Tunica Media
  • Tunica Intima
  • Swine
  • Signal Transduction
  • Polytetrafluoroethylene
  • Nerve Tissue Proteins
  • Models, Animal
  • Hyperplasia
  • Genetic Therapy
 

Citation

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Fields, R. C., Baig, K., Gaca, J., Milton, L. G., Koch, W. J., & Lawson, J. H. (2005). Reduction of vascular intimal-medial hyperplasia in polytetrafluoroethylene arteriovenous grafts via expression of an inhibitor of G protein signaling. Ann Vasc Surg, 19(5), 712–718. https://doi.org/10.1007/s10016-005-6805-9
Fields, Ryan C., Kamran Baig, Jeffrey Gaca, Luther G. Milton, Walter J. Koch, and Jeffrey H. Lawson. “Reduction of vascular intimal-medial hyperplasia in polytetrafluoroethylene arteriovenous grafts via expression of an inhibitor of G protein signaling.Ann Vasc Surg 19, no. 5 (September 2005): 712–18. https://doi.org/10.1007/s10016-005-6805-9.
Fields, Ryan C., et al. “Reduction of vascular intimal-medial hyperplasia in polytetrafluoroethylene arteriovenous grafts via expression of an inhibitor of G protein signaling.Ann Vasc Surg, vol. 19, no. 5, Sept. 2005, pp. 712–18. Pubmed, doi:10.1007/s10016-005-6805-9.
Journal cover image

Published In

Ann Vasc Surg

DOI

ISSN

0890-5096

Publication Date

September 2005

Volume

19

Issue

5

Start / End Page

712 / 718

Location

Netherlands

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Tunica Media
  • Tunica Intima
  • Swine
  • Signal Transduction
  • Polytetrafluoroethylene
  • Nerve Tissue Proteins
  • Models, Animal
  • Hyperplasia
  • Genetic Therapy