G Protein Signaling and Vein Graft Intimal Hyperplasia: Reduction of Intimal Hyperplasia in Vein Grafts by a Gbg Inhibitor

dc.contributor.author

Davies, MG

dc.contributor.author

Huynh, TT

dc.contributor.author

Fulton, GJ

dc.contributor.author

Lefkowitz, RJ

dc.contributor.author

Svendsen, E

dc.contributor.author

Hagen, PO

dc.contributor.author

Koch, WJ

dc.date.accessioned

2012-10-22T17:22:22Z

dc.date.available

2012-10-22T17:22:22Z

dc.date.issued

1998-08

dc.description.abstract

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 (Gβγ)–mediated activation of p21ras. This study examines the role of Gβγ signaling in intimal hyperplasia by targeting a gene encoding a specific Gβγ inhibitor in an experimental rabbit vein graft model. This inhibitor, the carboxyl terminus of the β-adrenergic receptor kinase (βARKCT), contains a Gβγ-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 βARKCT treatment. Thus, it appears that Gβγ-mediated pathways play a major role in intimal hyperplasia and that targeting inhibitors of Gβγ signaling offers novel intraoperative therapeutic modalities to inhibit the development of vein graft intimal hyperplasia and subsequent vein graft failure.

dc.identifier.citation

Davies, M. G., T. T. T. Huynh, et al. (1998). "G Protein Signaling and Vein Graft Intimal Hyperplasia." Arteriosclerosis, Thrombosis, and Vascular Biology 18(8): 1275-1280.

dc.identifier.uri

https://hdl.handle.net/10161/5903

dc.publisher

Ovid Technologies (Wolters Kluwer Health)

dc.relation.isversionof

10.1161/01.ATV.18.8.1275

dc.relation.journal

Arteriosclerosis, Thrombosis, and Vascular Biology

dc.subject

vein grafts

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carboxyl terminus of β-adrenergic receptor kinase

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gene transfer

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G proteins

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intimal hyperplasia

dc.title

G Protein Signaling and Vein Graft Intimal Hyperplasia: Reduction of Intimal Hyperplasia in Vein Grafts by a Gbg Inhibitor

dc.type

Journal article

duke.contributor.orcid

Lefkowitz, RJ|0000-0003-1472-7545

duke.contributor.orcid

Koch, WJ|0000-0002-8522-530X

duke.description.issue

8

duke.description.volume

18

pubs.begin-page

1275

pubs.end-page

1280

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