External support modulates G protein expression and receptor coupling in experimental vein grafts.
BACKGROUND
Intimal hyperplasia remains the leading cause of vein graft failure. Various external stenting devices have been shown to reduce the development of intimal hyperplasia in vein grafts. Mitogenic and mechanotransduction signals are known to be mediated by G protein-coupled receptors. Therefore in this study we examined the alterations in G protein expression and receptor coupling in vein grafts stented with external tube support.


METHODS
Thirty New Zealand White male rabbits had a right carotid interposition bypass graft with use of the ipsilateral jugular vein. Fifteen animals received external support and 15 were controls. In a subset the animals either had removal of the external support or a sham-control neck exploration at 14 days after the initial implantation (n = 5 per group).


RESULTS
External support reduced G alpha i3 proteins by 30% in vein grafts without changes in G alpha s by Western blot. Vein grafts with external support were significantly less sensitive to pertussis toxin inactivation than controls were in response to both norepinephrine and serotonin. A 24% decrease in intimal thickness was maintained after withdrawal of the initial external support.


CONCLUSIONS
The placement of an external support is associated with alternations in G protein expression and receptor coupling function in vein grafts. The results of this study suggest that the development of vein graft intimal hyperplasia may involve G protein-mediated events.
Huynh
T T
TT
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Iaccarino
G
G
Davies
M G
MG
Safi
H J
HJ
Koch
W J
WJ
Hagen
P O
PO
D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000032:analysis / Q000502:physiology*; D006965:Hyperplasia; D007601:Jugular Veins / Q000637:transplantation*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D012701:Serotonin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009638:Norepinephrine