PMID- 16308016
OWN - NLM
STAT- MEDLINE
DCOM- 20060321
LR  - 20121115
IS  - 1097-685X (Electronic)
IS  - 0022-5223 (Linking)
VI  - 130
IP  - 6
DP  - 2005 Dec
TI  - A Gbetagamma inhibitor reduces intimal hyperplasia in aortocoronary saphenous 
      vein grafts.
PG  - 1683-90
AB  - OBJECTIVE: Approximately 50% of aortocoronary saphenous vein grafts are occluded 
      10 years after coronary revascularization surgery. Intimal hyperplasia, a 
      critical component in saphenous vein graft failure, is defined by vascular smooth 
      muscle cell proliferation, which is mediated in part by betagamma subunits of 
      heterotrimeric G proteins (G(betagamma)) and downstream effectors such as 
      mitogen-activated protein kinases. A peptide consisting of the carboxyl-terminus 
      of the beta-adrenergic receptor kinase (betaARKct) binds G(betagamma), thereby 
      inhibiting G(betagamma) signaling. Utilizing a recombinant adenovirus containing 
      the coding sequence for the betaARKct peptide (AdbetaARKct), this study 
      investigates whether treatment of the vein graft with AdbetaARKct reduces intimal 
      hyperplasia in a large animal model of aortocoronary saphenous vein graft intimal 
      hyperplasia. METHODS: Twenty-seven dogs (27-32 kg) underwent aortocoronary bypass 
      grafting to the left anterior descending artery using autologous saphenous vein. 
      Vein grafts were treated with saline (n = 8), an empty adenovirus (n = 8), or 
      AdbetaARKct (n = 8). A subset of dogs (n = 3) were sacrificed on postoperative 
      day 7 and betaARKct expression confirmed by Northern blotting. RESULTS: 
      Arteriograms performed on postoperative day 90 confirmed that saphenous vein 
      grafts were patent. At postoperative day 90, AdbetaARKct-treated grafts 
      demonstrated reduced intimal area compared to empty virus and saline treated 
      animals (P < .05). Additionally, AdbetaARKct treatment of isolated vascular 
      smooth muscle cells in vitro inhibited mitogen-activated protein kinase 
      activation and decreased overall vascular smooth muscle cell proliferation. 
      CONCLUSION: This study demonstrates that betaARKct expression in aortocoronary 
      saphenous vein grafts reduces intimal hyperplasia and decreases vascular smooth 
      muscle cell proliferation in vitro via inhibition of G(betagamma)-mediated 
      mitogen-activated protein kinase activation. Modulation of G(betagamma) via 
      betaARKct may represent a novel therapy to reduce intimal hyperplasia and 
      saphenous vein graft failure.
FAU - Petrofski, Jason A
AU  - Petrofski JA
AD  - Surgery, Duke University Medical Center, Durham, NC 27703, USA.
FAU - Hata, Jonathan A
AU  - Hata JA
FAU - Williams, Matthew L
AU  - Williams ML
FAU - Parsa, Cyrus J
AU  - Parsa CJ
FAU - Thompson, Richard B
AU  - Thompson RB
FAU - Hanish, Steven I
AU  - Hanish SI
FAU - Gehrig, Thomas R
AU  - Gehrig TR
FAU - Koch, Walter J
AU  - Koch WJ
FAU - Milano, Carmelo A
AU  - Milano CA
LA  - eng
GR  - 5F32-HL-68437-02/HL/NHLBI NIH HHS/United States
GR  - 5F32H71387-2/PHS HHS/United States
GR  - HL072183-01AL/HL/NHLBI NIH HHS/United States
GR  - HL65360/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Thorac Cardiovasc Surg
JT  - The Journal of thoracic and cardiovascular surgery
JID - 0376343
RN  - 0 (Peptides)
RN  - 0 (Recombinant Proteins)
RN  - 0 (beta-adrenergic receptor kinase inhibitory peptide)
SB  - IM
MH  - Animals
MH  - *Coronary Artery Bypass
MH  - Dogs
MH  - *Genetic Therapy
MH  - Hyperplasia/prevention & control
MH  - Peptides/*therapeutic use
MH  - Recombinant Proteins/*therapeutic use
MH  - Saphenous Vein/*pathology/*transplantation
MH  - Tunica Intima/*pathology
EDAT- 2005/11/26 09:00
MHDA- 2006/03/22 09:00
CRDT- 2005/11/26 09:00
PHST- 2004/08/22 00:00 [received]
PHST- 2004/12/12 00:00 [revised]
PHST- 2005/01/10 00:00 [accepted]
PHST- 2005/11/26 09:00 [pubmed]
PHST- 2006/03/22 09:00 [medline]
PHST- 2005/11/26 09:00 [entrez]
AID - S0022-5223(05)01292-4 [pii]
AID - 10.1016/j.jtcvs.2005.01.024 [doi]
PST - ppublish
SO  - J Thorac Cardiovasc Surg. 2005 Dec;130(6):1683-90. doi: 
      10.1016/j.jtcvs.2005.01.024.