G protein signaling and vein graft intimal hyperplasia: reduction of intimal hyperplasia in vein grafts by a Gbetagamma inhibitor suggests a major role of G protein signaling in lesion development.

Journal Article (Journal Article)

Vein grafting results in the development of intimal hyperplasia with accompanying changes in guanine nucleotide-binding (G) protein expression and function. Several serum mitogens that act through G protein-coupled receptors, such as lysophosphatidic acid, stimulate proliferative pathways that are dependent on the G protein betagamma subunit (Gbetagamma)-mediated activation of p21ras. This study examines the role of Gbetagamma signaling in intimal hyperplasia by targeting a gene encoding a specific Gbetagamma inhibitor in an experimental rabbit vein graft model. This inhibitor, the carboxyl terminus of the beta-adrenergic receptor kinase (betaARK(CT)), contains a Gbetagamma-binding domain. Vein graft intimal hyperplasia was significantly reduced by 37% (P<0.01), and physiological studies demonstrated that the normal alterations in G protein coupling phenotypically seen in this model were blocked by betaARK(CT) treatment. Thus, it appears that Gbetagamma-mediated pathways play a major role in intimal hyperplasia and that targeting inhibitors of Gbetagamma signaling offers novel intraoperative therapeutic modalities to inhibit the development of vein graft intimal hyperplasia and subsequent vein graft failure.

Full Text

Duke Authors

Cited Authors

  • Davies, MG; Huynh, TT; Fulton, GJ; Lefkowitz, RJ; Svendsen, E; Hagen, PO; Koch, WJ

Published Date

  • August 1998

Published In

Volume / Issue

  • 18 / 8

Start / End Page

  • 1275 - 1280

PubMed ID

  • 9714134

International Standard Serial Number (ISSN)

  • 1079-5642

Digital Object Identifier (DOI)

  • 10.1161/01.atv.18.8.1275


  • eng

Conference Location

  • United States