Antibody to granulocyte macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function after myocardial infarction in a rat coronary artery ligation model

Robert S. Kellar, Jordan J. Lancaster, Hoang M. Thai, Elizabeth B Juneman, Nicholle M. Johnson, Howard G. Byrne, Maribeth Stansifer, Reza Arsanjani, Mark Baer, Christopher Bebbington, Michael Flashner, Geoffrey Yarranton, Steven Goldman

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Granulocyte macrophage colony-stimulating factor (GM-CSF) promotes infarct expansion and inappropriate collagen synthesis in a myocardial infarction (MI). This study was designed to determine if treatment with anti-GM-CSF will inhibit macrophage migration, preserve function, and limit left ventricular (LV) remodeling in the rat coronary artery ligation model. Treatment with a monoclonal antibody to GM-CSF (5 mg/kg) was initiated 24 hours before coronary artery ligation and continued every 3 days for 3 weeks. Left coronary arteries of rats were ligated, animals were recovered, and cardiac function was evaluated 3 weeks postligation. Tissue samples were processed for histochemistry. Anti-GM-CSF treatment increased LV ejection fraction (37 ± 3% vs 47 ± 5%) and decreased LV end systolic diameter (0.75 ± 0.12 vs 0.59 ± 0.05 cm) with no changes in LV systolic pressure (109 ± 4 vs 104 ± 5 mm Hg), LV end diastolic pressure (22 ± 4 vs 21 ± 2 mm Hg), LV end diastolic diameter (0.96 ± 0.04 vs 0.92 ± 0.05 cm), or the time constant of LV relaxation tau (25.4 ± +2.4 vs 22.7 ± 1.4 milliseconds) (P < 0.05). Significantly lower numbers of tissue macrophages and significant reductions in infarct size were found in the myocardium of antibody-treated animals (81 ± 21.24 vs 195 ± 31.7 positive cells per 0.105 mm, compared with controls. These findings suggest that inhibition of macrophage migration may be beneficial in the treatment of heart failure after MI.

Original languageEnglish (US)
Pages (from-to)568-574
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume57
Issue number5
DOIs
StatePublished - May 2011

Fingerprint

Granulocyte-Macrophage Colony-Stimulating Factor
Left Ventricular Function
Ligation
Coronary Vessels
Macrophages
Myocardial Infarction
Antibodies
Blood Pressure
Ventricular Remodeling
Ventricular Pressure
Treatment Failure
Stroke Volume
Myocardium
Collagen
Heart Failure
Monoclonal Antibodies

Keywords

  • activated macrophages
  • antibody
  • GM-CSF
  • granulocyte macrophage colony-stimulating factor
  • left ventricular function
  • myocardial infarction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Antibody to granulocyte macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function after myocardial infarction in a rat coronary artery ligation model. / Kellar, Robert S.; Lancaster, Jordan J.; Thai, Hoang M.; Juneman, Elizabeth B; Johnson, Nicholle M.; Byrne, Howard G.; Stansifer, Maribeth; Arsanjani, Reza; Baer, Mark; Bebbington, Christopher; Flashner, Michael; Yarranton, Geoffrey; Goldman, Steven.

In: Journal of Cardiovascular Pharmacology, Vol. 57, No. 5, 05.2011, p. 568-574.

Research output: Contribution to journalArticle

Kellar, Robert S. ; Lancaster, Jordan J. ; Thai, Hoang M. ; Juneman, Elizabeth B ; Johnson, Nicholle M. ; Byrne, Howard G. ; Stansifer, Maribeth ; Arsanjani, Reza ; Baer, Mark ; Bebbington, Christopher ; Flashner, Michael ; Yarranton, Geoffrey ; Goldman, Steven. / Antibody to granulocyte macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function after myocardial infarction in a rat coronary artery ligation model. In: Journal of Cardiovascular Pharmacology. 2011 ; Vol. 57, No. 5. pp. 568-574.
@article{2a071a2f51c74b528b4f323fa31e43f2,
title = "Antibody to granulocyte macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function after myocardial infarction in a rat coronary artery ligation model",
abstract = "Granulocyte macrophage colony-stimulating factor (GM-CSF) promotes infarct expansion and inappropriate collagen synthesis in a myocardial infarction (MI). This study was designed to determine if treatment with anti-GM-CSF will inhibit macrophage migration, preserve function, and limit left ventricular (LV) remodeling in the rat coronary artery ligation model. Treatment with a monoclonal antibody to GM-CSF (5 mg/kg) was initiated 24 hours before coronary artery ligation and continued every 3 days for 3 weeks. Left coronary arteries of rats were ligated, animals were recovered, and cardiac function was evaluated 3 weeks postligation. Tissue samples were processed for histochemistry. Anti-GM-CSF treatment increased LV ejection fraction (37 ± 3{\%} vs 47 ± 5{\%}) and decreased LV end systolic diameter (0.75 ± 0.12 vs 0.59 ± 0.05 cm) with no changes in LV systolic pressure (109 ± 4 vs 104 ± 5 mm Hg), LV end diastolic pressure (22 ± 4 vs 21 ± 2 mm Hg), LV end diastolic diameter (0.96 ± 0.04 vs 0.92 ± 0.05 cm), or the time constant of LV relaxation tau (25.4 ± +2.4 vs 22.7 ± 1.4 milliseconds) (P < 0.05). Significantly lower numbers of tissue macrophages and significant reductions in infarct size were found in the myocardium of antibody-treated animals (81 ± 21.24 vs 195 ± 31.7 positive cells per 0.105 mm, compared with controls. These findings suggest that inhibition of macrophage migration may be beneficial in the treatment of heart failure after MI.",
keywords = "activated macrophages, antibody, GM-CSF, granulocyte macrophage colony-stimulating factor, left ventricular function, myocardial infarction",
author = "Kellar, {Robert S.} and Lancaster, {Jordan J.} and Thai, {Hoang M.} and Juneman, {Elizabeth B} and Johnson, {Nicholle M.} and Byrne, {Howard G.} and Maribeth Stansifer and Reza Arsanjani and Mark Baer and Christopher Bebbington and Michael Flashner and Geoffrey Yarranton and Steven Goldman",
year = "2011",
month = "5",
doi = "10.1097/FJC.0b013e318213258b",
language = "English (US)",
volume = "57",
pages = "568--574",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Antibody to granulocyte macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function after myocardial infarction in a rat coronary artery ligation model

AU - Kellar, Robert S.

AU - Lancaster, Jordan J.

AU - Thai, Hoang M.

AU - Juneman, Elizabeth B

AU - Johnson, Nicholle M.

AU - Byrne, Howard G.

AU - Stansifer, Maribeth

AU - Arsanjani, Reza

AU - Baer, Mark

AU - Bebbington, Christopher

AU - Flashner, Michael

AU - Yarranton, Geoffrey

AU - Goldman, Steven

PY - 2011/5

Y1 - 2011/5

N2 - Granulocyte macrophage colony-stimulating factor (GM-CSF) promotes infarct expansion and inappropriate collagen synthesis in a myocardial infarction (MI). This study was designed to determine if treatment with anti-GM-CSF will inhibit macrophage migration, preserve function, and limit left ventricular (LV) remodeling in the rat coronary artery ligation model. Treatment with a monoclonal antibody to GM-CSF (5 mg/kg) was initiated 24 hours before coronary artery ligation and continued every 3 days for 3 weeks. Left coronary arteries of rats were ligated, animals were recovered, and cardiac function was evaluated 3 weeks postligation. Tissue samples were processed for histochemistry. Anti-GM-CSF treatment increased LV ejection fraction (37 ± 3% vs 47 ± 5%) and decreased LV end systolic diameter (0.75 ± 0.12 vs 0.59 ± 0.05 cm) with no changes in LV systolic pressure (109 ± 4 vs 104 ± 5 mm Hg), LV end diastolic pressure (22 ± 4 vs 21 ± 2 mm Hg), LV end diastolic diameter (0.96 ± 0.04 vs 0.92 ± 0.05 cm), or the time constant of LV relaxation tau (25.4 ± +2.4 vs 22.7 ± 1.4 milliseconds) (P < 0.05). Significantly lower numbers of tissue macrophages and significant reductions in infarct size were found in the myocardium of antibody-treated animals (81 ± 21.24 vs 195 ± 31.7 positive cells per 0.105 mm, compared with controls. These findings suggest that inhibition of macrophage migration may be beneficial in the treatment of heart failure after MI.

AB - Granulocyte macrophage colony-stimulating factor (GM-CSF) promotes infarct expansion and inappropriate collagen synthesis in a myocardial infarction (MI). This study was designed to determine if treatment with anti-GM-CSF will inhibit macrophage migration, preserve function, and limit left ventricular (LV) remodeling in the rat coronary artery ligation model. Treatment with a monoclonal antibody to GM-CSF (5 mg/kg) was initiated 24 hours before coronary artery ligation and continued every 3 days for 3 weeks. Left coronary arteries of rats were ligated, animals were recovered, and cardiac function was evaluated 3 weeks postligation. Tissue samples were processed for histochemistry. Anti-GM-CSF treatment increased LV ejection fraction (37 ± 3% vs 47 ± 5%) and decreased LV end systolic diameter (0.75 ± 0.12 vs 0.59 ± 0.05 cm) with no changes in LV systolic pressure (109 ± 4 vs 104 ± 5 mm Hg), LV end diastolic pressure (22 ± 4 vs 21 ± 2 mm Hg), LV end diastolic diameter (0.96 ± 0.04 vs 0.92 ± 0.05 cm), or the time constant of LV relaxation tau (25.4 ± +2.4 vs 22.7 ± 1.4 milliseconds) (P < 0.05). Significantly lower numbers of tissue macrophages and significant reductions in infarct size were found in the myocardium of antibody-treated animals (81 ± 21.24 vs 195 ± 31.7 positive cells per 0.105 mm, compared with controls. These findings suggest that inhibition of macrophage migration may be beneficial in the treatment of heart failure after MI.

KW - activated macrophages

KW - antibody

KW - GM-CSF

KW - granulocyte macrophage colony-stimulating factor

KW - left ventricular function

KW - myocardial infarction

UR - http://www.scopus.com/inward/record.url?scp=79957687825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957687825&partnerID=8YFLogxK

U2 - 10.1097/FJC.0b013e318213258b

DO - 10.1097/FJC.0b013e318213258b

M3 - Article

C2 - 21326109

AN - SCOPUS:79957687825

VL - 57

SP - 568

EP - 574

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 5

ER -