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Potentiel thérapeutique des S-nitrosothiols dans la prévention de l’athérosclérose : modulation de la métaplasie des monocytes et cellules musculaires lisses en cellules spumeuses

Abstract : Atherosclerosis is a chronic disease, quiet, with a slow evolution, characterized by the formation of atherosclerotic plaques. These are formed further to an accumulation of low-density lipoproteins (LDLs), monocytes and smooth muscle cells (SMCs), followed by their metaplasia into foam cells. The whole leads to the formation of the necrotic core and a possible artery calcification. The evolution of these phenomena is due to a combination of inflammation and oxidative stress. Two major cell types are involved in atherosclerotic plaques formation: i) monocytes, differentiated into two sub-populations of macrophages: pro-inflammatory (M1) and anti-inflammatory (M2) as well as ii) SMCs, losing their contractile phenotype to dedifferentiate into a secretory/proliferative phenotype. Differentiated/dedifferentiated cells purchase the capacity to internalize oxidized LDLs (oxLDLs), allowing foam cells formation. Oxidative stress and inflammation cause also an endothelial dysfunction leading to a decrease of nitric oxide (NO) bioavailability, LDLs oxidation and a proliferation/dedifferentiation of SMCs. In order to compensate this decrease of NO, the use of NO donors, such as S-nitrosothiols, is considered. Formed by S-nitrosation, they increase NO half-life and limit oxidative stress. Among them, S-nitrosoglutathione (GSNO), a physiological storage form and transport of NO, allows to mimic physiological reservoirs of NO. The first part of this manuscript was devoted to the development of a cellular model of monocytes/macrophages differentiation followed by their polarization into M1- and M2-macrophages. The second part of this manuscript was centred on the study of the impact of NO, and more specifically of GSNO, on foam cells formation. Finally, in a third part, the development of a cellular model of SMC dedifferentiation from a stimulus inducing oxidative stress, angiotensin II.
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https://hal.univ-lorraine.fr/tel-03559981
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Submitted on : Monday, February 7, 2022 - 11:56:00 AM
Last modification on : Tuesday, February 8, 2022 - 3:37:18 AM
Long-term archiving on: : Sunday, May 8, 2022 - 6:37:21 PM

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  • HAL Id : tel-03559981, version 1

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Justine Bonetti. Potentiel thérapeutique des S-nitrosothiols dans la prévention de l’athérosclérose : modulation de la métaplasie des monocytes et cellules musculaires lisses en cellules spumeuses. Médecine humaine et pathologie. Université de Lorraine; Università degli studi (Sienne, Italie), 2021. Français. ⟨NNT : 2021LORR0172⟩. ⟨tel-03559981⟩

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