Granulocyte-Macrophage Colony–Stimulating Factor Prevents the Progression of Atherosclerosis via Changes in the Cellular and Extracellular Composition of Atherosclerotic Lesions in Watanabe Heritable Hyperlipidemic Rabbits

Abstract

Background —A cytokine network is involved in atherogenesis. This study was conducted to investigate the effects of granulocyte-macrophage colony–stimulating factor (GM-CSF) on the development and composition of atherosclerotic lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits. Methods and Results —GM-CSF (10 μg · kg ⁻¹ · d ⁻¹ ) was administered to 4-month-old WHHL rabbits (n=9) 5 days a week for 7.5 months, whereas an equal dose of human serum albumin was administered to controls (n=9). The cholesterol levels were not changed significantly by the treatment. Age-matched 4-month-old rabbits (n=7) had atheromatous plaques over 30.7±5.7% of the inner surface area of the aortic arch. After treatment, the percentages of surface atheromatous plaques to total aortic arch area were 45.0±12.6% in the GM-CSF group and 74.3±11.0% in controls ( P P P P =0.0001), collagen ( P =0.0001), and extracellular lipid deposits ( P P P Conclusions —GM-CSF altered the composition of atherosclerotic lesions and reduced the atherosclerosis in WHHL rabbits.