La semicarbazide-sensitive amine oxydase : son rôle dans la différenciation cellulaire des chondrocytes et des cellules musculaires lisses vasculaires et son implication dans des pathologies articulaires et cardiovasculaires

Abstract : The semicarbazide-sensitive amine oxidase (SSAO) catalyzes the oxidative deamination of primary amines into aldehydes, hydrogen peroxide and ammonia. The SSAO was implicated in cellular differentiation, inflammation and transmigration of leukocyte through the lymphatic. The objectives of this work were to study the role of SSAO (i) in chondrocyte differentiation and in the development of osteoarthritis using rat chondrocyte primary cell culture and osteroarthritic samples from patients. (ii) in the development of atherosclerosis using ApoE-/- mice, which develop naturally atherosclerosis, invalidated for the SSAO gene. Concerning the articulation, the SSAO (expression and activity) was detected in the rat and human cartilage. In vitro, SSAO increases during chondrocyte terminal differentiation (hypertrophy) and the inhibition of its activity by LJP1586, decreases the level of differentiation. In human arthritic cartilage, SSAO was higher that in healthy cartilage, in association with an increase in hypertrophic markers. The SSAO plays a role in the terminal differentiation of chondrocytes and might be involved in the development of osteoarthritis. At the vascular level, 25 week-old female ApoE-/-SSAO-/- mice presented a 50% increase in plaque surface associated with an 80% decrease in [alpha]-actin expression in the media of aortic sinus and a decrease in sm-MCH in abdominal aortas (AA) compared to ApoE-/- mice. These results were not due neither to a modification of monocytes/ macrophages, Tcell infiltration in the plaque nor in a pro- or anti-inflammatory cytokine change in spleen. In 15 week-old ApoE-/-SSAO-/- mice, even if no modification of plaque surface was found, a decrease in sm-MHC was noticed in the AA from ApoE-/-SSAO-/- compare to ApoE-/- mice. More over, the immune cell trafficking was increased in the aortic wall of ApoE-/-SSAO-/- compared to ApoE-/- mice. Thus, SSAO is involved in the early development of atherosclerosis in changing the immune cell trafficking and the VSMC phenotype
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Anna Filip. La semicarbazide-sensitive amine oxydase : son rôle dans la différenciation cellulaire des chondrocytes et des cellules musculaires lisses vasculaires et son implication dans des pathologies articulaires et cardiovasculaires. Human health and pathology. Université de Lorraine, 2014. English. ⟨NNT : 2014LORR0244⟩. ⟨tel-01751265⟩

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