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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.
- 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.
- Subjects :
- Analysis of Variance
Animals
Base Sequence
Cyclic AMP-Dependent Protein Kinases genetics
GTP-Binding Proteins antagonists & inhibitors
GTP-Binding Proteins drug effects
Gene Expression Regulation, Enzymologic physiology
Gene Transfer Techniques
Hyperplasia metabolism
Hyperplasia pathology
Hyperplasia prevention & control
Microscopy, Electron, Scanning
Molecular Sequence Data
Phenotype
Rabbits
Signal Transduction drug effects
Statistics, Nonparametric
Transgenes genetics
Tunica Intima metabolism
Tunica Intima ultrastructure
Veins drug effects
Veins metabolism
Veins ultrastructure
beta-Adrenergic Receptor Kinases
Cyclic AMP-Dependent Protein Kinases pharmacology
GTP-Binding Proteins metabolism
Peptide Fragments pharmacology
Recombinant Proteins
Signal Transduction physiology
Tunica Intima drug effects
Veins transplantation
Subjects
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