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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.

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.

Authors :
Davies MG
Huynh TT
Fulton GJ
Lefkowitz RJ
Svendsen E
Hagen PO
Koch WJ
Source :
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 1998 Aug; Vol. 18 (8), pp. 1275-80.
Publication Year :
1998

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 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.

Details

Language :
English
ISSN :
1079-5642
Volume :
18
Issue :
8
Database :
MEDLINE
Journal :
Arteriosclerosis, thrombosis, and vascular biology
Publication Type :
Academic Journal
Accession number :
9714134
Full Text :
https://doi.org/10.1161/01.atv.18.8.1275