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

Article

关键词: MONOCYTE-DERIVED MACROPHAGES;    CHOLESTEROL-LOWERING ACTIVITY;    SMOOTH-MUSCLE CELLS;    MESSENGER-RNA;    RECEPTOR;    CORONARY;    PROBUCOL;    HYPERCHOLESTEROLEMIA;    DEGRADATION;    EXPRESSION;   

DOI  :  10.1161/01.CIR.99.16.2150

来源: SCIE

【 摘 要 】

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 anti Results-GM-CSF(10 mu g.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<0.0001), Histological examination demonstrated that GM-CSF reduced the ratio of intima to media (P<0.01) and cross-sectional areas of atherosclerotic lesions (P<0.0001); Quantitative analysis indicated a marked decrease in the areas of smooth muscle cells (P=0.0001), collagen (P=0.0001), and extracellular lipid deposits (P<0.05) of atheromatous plaques in:GM-CSF treated rabbits compared with controls. The terminal deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method and immunohistochemistry were performed to examine the relationship between decreased atherosclerotic lesions and apoptosis., The percentage of TUNEL-positive cells increased in the: GM-CSF group (GM-CF, 24.1+/-4.4% versus control, 11.6+/-3.2%; P<0.0001). GM-CSF enhanced the apoptosis of smooth muscle cells in the shoulder region and the fibrous cap (P<0.0001), suggesting one of the mechanisms for the antiatherogenic effect. Conclusions-GM-CSF altered the composition of atherosclerotic lesions and reduced the atherosclerosis in WHHL rabbits.

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