Rôle des exosomes dans la dysfonction endothéliale associée au syndrome métabolique

Abstract : Metabolic syndrome (MetS) is defined as the combination of metabolic disorders leading to cardiovascular diseases and the development of type 2 diabetes. To be diagnosed with MetS, a person must present at least 3 of the following 5 metabolic risk factors: (i) abdominal obesity, (ii) high triglyceride levels,(iii) low HDL cholesterol levels, (iv) hypertension and (v) hyperglycaemia. MetS is characterized by endothelial dysfunction, which is defined by a decreased nitric oxide (NO) production, and an increased in reactive oxygen species such as superoxide (O2-), involved in oxidative stress. In our study, we hypothesized that exosomes could participate in the endothelial dysfunction observed in MetS patients. Exosomes are nanoscaled (30-100nm) extracellular vesicles produced from the endolysosomal compartment and released by most of the cells of the organism. Following their release, they can interact with their target cells and be considered as biological information carriers. Exosomes have been shown to be involved in many pathologies. Thus, we have shown that MetS patients displayed an increased circulating rate of exosomes whose sizes were decreased. In addition, we have observed that exosomes from MetS patients induced (i) a decrease of NO production in endothelial cells, and (ii) an increase in mitochondrial O2-. Furthermore, the exosomes originating from MetS patients induced a decrease invascular relaxation in mice. Thus, the exosomes could participate in the development of endothelial dysfunction in MetS patients and could be considered as biomarkers of interest for this pathology.
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Marine Malloci. Rôle des exosomes dans la dysfonction endothéliale associée au syndrome métabolique. Médecine humaine et pathologie. Université d'Angers, 2017. Français. ⟨NNT : 2017ANGE0076⟩. ⟨tel-02285898⟩

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