Abstract

Objective: The endogenous opioid [Met5]-enkephalin (opioid growth factor [OGF]) is a tonically active, receptor-mediated inhibitory growth peptide in developing and adult vasculature. This study was designed to determine the role of OGF in neointimal hyperplasia. Methods: The carotid artery in adult male Sprague-Dawley rats was denuded with balloon catheterization. OGF (10 mg/kg), the opioid antagonist naltrexone (NTX; 30 mg/kg), or saline solution (0.2 mL) was injected intraperitoneally daily for 28 days into the rats, and restenosis of the carotid artery was examined with morphometric analysis using Optimas software. Proliferation of the neointima and media was measured by radioactive thymidine incorporation over 3 hours. The presence of OGF and its receptor, OGFr, were examined with immunofluorescence microscopy. Results: OGF depressed DNA synthesis in the intima and media from 16% to 78% of control levels in the first 2 weeks after deendothelialization, whereas NTX exposure elevated DNA synthesis by 21% to 89%. OGF action was receptor-mediated. In the month after injury the thickness of the intima in OGF-treated rats was decreased by 18% to 31% from control values, whereas intimal thickness was increased in the NTX group by 10% to 31%. Luminal area was almost 25% greater than control values in the OGF group, but was reduced 17% by NTX. OGF and the OGF receptor were detected in the carotid artery with immunohistochemistry. Conclusions: These results demonstrate for the first time that a native opioid system modulates repair of vascular injury. OGF is a constitutively active peptide that has a receptor-mediated action in the negative regulation of neointimal growth, a major cause of restenosis.

Original languageEnglish (US)
Pages (from-to)636-643
Number of pages8
JournalJournal of Vascular Surgery
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Tunica Intima
Carotid Arteries
Opioid Analgesics
Hyperplasia
Intercellular Signaling Peptides and Proteins
Neointima
Peptides
Naltrexone
Narcotic Antagonists
Enkephalins
Vascular System Injuries
DNA
Growth
Fluorescence Microscopy
Sodium Chloride
Catheterization
Thymidine
Sprague Dawley Rats
Software

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

@article{9826ba6ae9df44af9a19dc7a75db3d96,
title = "Opioid growth factor inhibits intimal hyperplasia in balloon-injured rat carotid artery",
abstract = "Objective: The endogenous opioid [Met5]-enkephalin (opioid growth factor [OGF]) is a tonically active, receptor-mediated inhibitory growth peptide in developing and adult vasculature. This study was designed to determine the role of OGF in neointimal hyperplasia. Methods: The carotid artery in adult male Sprague-Dawley rats was denuded with balloon catheterization. OGF (10 mg/kg), the opioid antagonist naltrexone (NTX; 30 mg/kg), or saline solution (0.2 mL) was injected intraperitoneally daily for 28 days into the rats, and restenosis of the carotid artery was examined with morphometric analysis using Optimas software. Proliferation of the neointima and media was measured by radioactive thymidine incorporation over 3 hours. The presence of OGF and its receptor, OGFr, were examined with immunofluorescence microscopy. Results: OGF depressed DNA synthesis in the intima and media from 16{\%} to 78{\%} of control levels in the first 2 weeks after deendothelialization, whereas NTX exposure elevated DNA synthesis by 21{\%} to 89{\%}. OGF action was receptor-mediated. In the month after injury the thickness of the intima in OGF-treated rats was decreased by 18{\%} to 31{\%} from control values, whereas intimal thickness was increased in the NTX group by 10{\%} to 31{\%}. Luminal area was almost 25{\%} greater than control values in the OGF group, but was reduced 17{\%} by NTX. OGF and the OGF receptor were detected in the carotid artery with immunohistochemistry. Conclusions: These results demonstrate for the first time that a native opioid system modulates repair of vascular injury. OGF is a constitutively active peptide that has a receptor-mediated action in the negative regulation of neointimal growth, a major cause of restenosis.",
author = "Ian Zagon and Essis, {Frank M.} and Michael Verderame and Healy, {Dean A.} and Robert Atnip and Patricia McLaughlin",
year = "2003",
month = "3",
day = "1",
doi = "10.1067/mva.2003.165",
language = "English (US)",
volume = "37",
pages = "636--643",
journal = "Journal of Vascular Surgery",
issn = "0741-5214",
publisher = "Mosby Inc.",
number = "3",

}

Opioid growth factor inhibits intimal hyperplasia in balloon-injured rat carotid artery. / Zagon, Ian; Essis, Frank M.; Verderame, Michael; Healy, Dean A.; Atnip, Robert; McLaughlin, Patricia.

In: Journal of Vascular Surgery, Vol. 37, No. 3, 01.03.2003, p. 636-643.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Opioid growth factor inhibits intimal hyperplasia in balloon-injured rat carotid artery

AU - Zagon, Ian

AU - Essis, Frank M.

AU - Verderame, Michael

AU - Healy, Dean A.

AU - Atnip, Robert

AU - McLaughlin, Patricia

PY - 2003/3/1

Y1 - 2003/3/1

N2 - Objective: The endogenous opioid [Met5]-enkephalin (opioid growth factor [OGF]) is a tonically active, receptor-mediated inhibitory growth peptide in developing and adult vasculature. This study was designed to determine the role of OGF in neointimal hyperplasia. Methods: The carotid artery in adult male Sprague-Dawley rats was denuded with balloon catheterization. OGF (10 mg/kg), the opioid antagonist naltrexone (NTX; 30 mg/kg), or saline solution (0.2 mL) was injected intraperitoneally daily for 28 days into the rats, and restenosis of the carotid artery was examined with morphometric analysis using Optimas software. Proliferation of the neointima and media was measured by radioactive thymidine incorporation over 3 hours. The presence of OGF and its receptor, OGFr, were examined with immunofluorescence microscopy. Results: OGF depressed DNA synthesis in the intima and media from 16% to 78% of control levels in the first 2 weeks after deendothelialization, whereas NTX exposure elevated DNA synthesis by 21% to 89%. OGF action was receptor-mediated. In the month after injury the thickness of the intima in OGF-treated rats was decreased by 18% to 31% from control values, whereas intimal thickness was increased in the NTX group by 10% to 31%. Luminal area was almost 25% greater than control values in the OGF group, but was reduced 17% by NTX. OGF and the OGF receptor were detected in the carotid artery with immunohistochemistry. Conclusions: These results demonstrate for the first time that a native opioid system modulates repair of vascular injury. OGF is a constitutively active peptide that has a receptor-mediated action in the negative regulation of neointimal growth, a major cause of restenosis.

AB - Objective: The endogenous opioid [Met5]-enkephalin (opioid growth factor [OGF]) is a tonically active, receptor-mediated inhibitory growth peptide in developing and adult vasculature. This study was designed to determine the role of OGF in neointimal hyperplasia. Methods: The carotid artery in adult male Sprague-Dawley rats was denuded with balloon catheterization. OGF (10 mg/kg), the opioid antagonist naltrexone (NTX; 30 mg/kg), or saline solution (0.2 mL) was injected intraperitoneally daily for 28 days into the rats, and restenosis of the carotid artery was examined with morphometric analysis using Optimas software. Proliferation of the neointima and media was measured by radioactive thymidine incorporation over 3 hours. The presence of OGF and its receptor, OGFr, were examined with immunofluorescence microscopy. Results: OGF depressed DNA synthesis in the intima and media from 16% to 78% of control levels in the first 2 weeks after deendothelialization, whereas NTX exposure elevated DNA synthesis by 21% to 89%. OGF action was receptor-mediated. In the month after injury the thickness of the intima in OGF-treated rats was decreased by 18% to 31% from control values, whereas intimal thickness was increased in the NTX group by 10% to 31%. Luminal area was almost 25% greater than control values in the OGF group, but was reduced 17% by NTX. OGF and the OGF receptor were detected in the carotid artery with immunohistochemistry. Conclusions: These results demonstrate for the first time that a native opioid system modulates repair of vascular injury. OGF is a constitutively active peptide that has a receptor-mediated action in the negative regulation of neointimal growth, a major cause of restenosis.

UR - http://www.scopus.com/inward/record.url?scp=0037347539&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037347539&partnerID=8YFLogxK

U2 - 10.1067/mva.2003.165

DO - 10.1067/mva.2003.165

M3 - Article

C2 - 12618704

AN - SCOPUS:0037347539

VL - 37

SP - 636

EP - 643

JO - Journal of Vascular Surgery

JF - Journal of Vascular Surgery

SN - 0741-5214

IS - 3

ER -