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Abstract: P682 GENETIC DELETION OF OX40 LIGAND SUPPRESSES THE DEVELOPMENT OF ATHEROSCLEROSIS IN APOLIPOPROTEIN EDEFICIENT MICE
Poster - BASIC SCIENCE - Inflammation Abstract: P682 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
GENETIC DELETION OF OX40 LIGAND SUPPRESSES THE DEVELOPMENT OF ATHEROSCLEROSIS IN APOLIPOPROTEIN EDEFICIENT MICE M Nakano1, Y Fukumoto1, K Satoh1, N Ishii2, K Sugamura2, H Shimokawa1 1
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai; 2Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai Background: Atherosclerosis is characterized by infiltration of inflammatory cells, for which immunological mechanism may be involved. It has been demonstrated that atherosclerosis is associated with enhanced vasa vasorum formation.OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is expressed in activated T-cells, while OX40 ligand (OX40L) is expressed in activated macrophages and endothelial cells. In this study, we examined whether OX40/OX40L system is involved in the pathogenesis of atherosclerosis. Method and results: We first demonstrated that endothelial cells in human coronary atheroma were immunopositive for OX40L (n=5). We then examined whether the OX40/OX40L system influences the atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. ApoE-/- mice and ApoE-/-/OX40L-deficient (ApoE-/-/OX40L-/-) mice were fed on a high-fat diet starting at 4 weeks of age. After 8 weeks, oil-red O staining of aorta demonstrated that the extent of atheroma was significantly less in ApoE-/-/OX40L-/- mice as compared with ApoE-/- mice (9.6±2.2%vs.13.6±3.5%,P<0.01). To elucidate the role of OX40L in vasa vasorum formation, we examined adventitial vascularity by immunostaining and confirmed that the number of blood vessels was significantly less in ApoE-/-/OX40L-/- mice as compared with ApoE-/- mice (16.0±3.2vs.33.5±16.1 vessels/HPF,P<0.01,n=8). Conclusions: These results indicate that the OX40/OX40L system could be a new therapeutic target for atherosclerosis through inhibition of neovascularization in atheroma.
GENETIC DELETION OF OX40 LIGAND SUPPRESSES THE DEVELOPMENT OF ATHEROSCLEROSIS IN APOLIPOPROTEIN EDEFICIENT MICE M Nakano1, Y Fukumoto1, K Satoh1, N Ishii2, K Sugamura2, H Shimokawa1 1
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai; 2Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai Background: Atherosclerosis is characterized by infiltration of inflammatory cells, for which immunological mechanism may be involved. It has been demonstrated that atherosclerosis is associated with enhanced vasa vasorum formation.OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is expressed in activated T-cells, while OX40 ligand (OX40L) is expressed in activated macrophages and endothelial cells. In this study, we examined whether OX40/OX40L system is involved in the pathogenesis of atherosclerosis. Method and results: We first demonstrated that endothelial cells in human coronary atheroma were immunopositive for OX40L (n=5). We then examined whether the OX40/OX40L system influences the atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. ApoE-/- mice and ApoE-/-/OX40L-deficient (ApoE-/-/OX40L-/-) mice were fed on a high-fat diet starting at 4 weeks of age. After 8 weeks, oil-red O staining of aorta demonstrated that the extent of atheroma was significantly less in ApoE-/-/OX40L-/- mice as compared with ApoE-/- mice (9.6±2.2%vs.13.6±3.5%,P<0.01). To elucidate the role of OX40L in vasa vasorum formation, we examined adventitial vascularity by immunostaining and confirmed that the number of blood vessels was significantly less in ApoE-/-/OX40L-/- mice as compared with ApoE-/- mice (16.0±3.2vs.33.5±16.1 vessels/HPF,P<0.01,n=8). Conclusions: These results indicate that the OX40/OX40L system could be a new therapeutic target for atherosclerosis through inhibition of neovascularization in atheroma.