G protein signaling and vein graft intimal hyperplasia: Reduction of intimal hyperplasia in vein grafts by a G(βγ) inhibitor suggests a major role of G protein signaling in lesion development

Mark G. Davies, Tam T.T. Huynh, Gregory J. Fulton, Robert J. Lefkowitz, Einar Svendsen, Per Otto Hagen, Walter J. Koch

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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 βγ subunit (G(βγ))-mediated activation of p21(ras). This study examines the role of G(βγ) signaling in intimal hyperplasia by targeting a gene encoding a specific G(βγ) inhibitor in an experimental rabbit vein graft model. This inhibitor, the carboxyl terminus of the β-adrenergic receptor kinase (βARK(CT)), contains a G(βγ)-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 βARK(CT) treatment. Thus, it appears that G(βγ)-mediated pathways play a major role in intimal hyperplasia and that targeting inhibitors of G(βγ) signaling offers novel intraoperative therapeutic modalities to inhibit the development of vein graft intimal hyperplasia and subsequent vein graft failure.

Original languageEnglish (US)
Pages (from-to)1275-1280
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume18
Issue number8
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Carboxyl terminus of β-adrenergic receptor kinase
  • G proteins
  • Gene transfer
  • Intimal hyperplasia
  • Vein grafts

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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