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Effets à long terme de l'atorvastatine à faible dose sur l'athérosclérose : une étude pluridisciplinaire chez un modèle animal, le lapin Watanabe

Abstract : Cardiovascular diseases are the first worldwide causes of death, associated to the presence and rupture of atherosclerotic plaques. To limit acute events, statins may be prescribed. However, its use leads to deleterious effects risk. To reduce this risk, a dose reduction could be considered. The work of this thesis is to study potential effects of a very low dose of atorvastatin, taken in the long term, in an animal model: the Watanabe rabbit. Measurements are made on control and treated animals from the age of 3 to 12 months. Circulating lipids, biochemical parameters and parameters of adhesion and inflammation were studied. Atherosclerosis evolution was evaluated by optical coherence tomography (OCT). Histological measurements allowed to validate a ranking proposed with OCT observations and to quantify intra-plaque macrophage content. Arterial stiffness was tested in vivo with pulse wave velocity and in vitro with a static tensile test. Vascular function was approached with vasoreactivity in different territories (aorta, carotid, mesenteric). Elastin and collagen contents of the artery wall were determined with two-photon and second harmonic generation microscopy. Finally, mitochondrial respiration and its susceptibility to ROS were evaluated in permeabilized cardiac fibers, any enzymatic antioxidant systems and lipid peroxidation were measured. Results show beneficial effects of this very low dose atorvastatin treatment in cardiovascular function, independently of a lipid-lowering effect.Keywords: atherosclerosis,
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https://tel.archives-ouvertes.fr/tel-01997610
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Florine Tissier. Effets à long terme de l'atorvastatine à faible dose sur l'athérosclérose : une étude pluridisciplinaire chez un modèle animal, le lapin Watanabe. Santé. Université de Bretagne occidentale - Brest, 2015. Français. ⟨NNT : 2015BRES0076⟩. ⟨tel-01997610⟩

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