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

• Published in: Journal of cardiovascular pharmacology Vol. 57; no. 5; pp. 568 - 574
• Main Authors: Kellar, Robert S, Lancaster, Jordan J, Thai, Hoang M, Juneman, Elizabeth, Johnson, Nicholle M, Byrne, Howard G, Stansifer, Maribeth, Arsanjani, Reza, Baer, Mark, Bebbington, Christopher, Flashner, Michael, Yarranton, Geoffrey, Goldman, Steven
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins, Inc 01-05-2011
• Subjects: Animals; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antibodies, Monoclonal, Murine-Derived - pharmacology; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Cell Count; Cell Movement - drug effects; Coronary Vessels - immunology; Coronary Vessels - pathology; Disease Models, Animal; Granulocyte-Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Hemodynamics - drug effects; Macrophage Activation - drug effects; Macrophage Activation - immunology; Macrophages - cytology; Macrophages - drug effects; Macrophages - immunology; Male; Myocardial Infarction - drug therapy; Myocardial Infarction - immunology; Myocardial Infarction - physiopathology; Rats; Rats, Sprague-Dawley; Ventricular Function, Left - drug effects; Ventricular Remodeling - drug effects
• ISSN: 0160-2446; 1533-4023
• DOI: 10.1097/FJC.0b013e318213258b

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.