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Caractérisation protéomique du matrisome des maladies des petits vaisseaux cérébraux par spectrométrie de masse

Abstract : Diseases of the small vessels of the brain are responsible for damage to the white matter of the brain and multiple deep braininfarctions. They are the cause of more than 25% of strokes and are the second cause of dementia after Alzheimer's dementia. It is aset of pathological processes, which affect small arteries, arterioles, cerebral venule or capillary of less than 400µm. Thecerebrovascular matrisome seems to be a converging pathological pathway between the various diseases of the small vessels of thegenetic type and of the sporadic type. The matrisome is the set of proteins constituting the extracellular matrix (ECM) as well as theassociated proteins, their roles consist not only in the support and the anchoring of the cells but also in various fundamental processessuch as differentiation, proliferation, Survival or migration of cells. The structural and physico-chemical diversity of these proteins,however, makes their analysis particularly delicate. Within the framework of this thesis we propose to characterize in a quantitativeand qualitative way the microvascular matrisome in the diseases of the small vessels, as well as to identify commonabnormalities orspecific to each disease. For this we have developed a label-free quantitative proteomic approach on cerebral and peripheral vesselsisolated from three preclinical genetic murine models and two murine models for the sporadic character. We have developed andvalidated a new robust and sensitive method for the quantitative non-labeling analysis of changes in the matrisome of mouse cerebralarteries and the application of our method on the arteries of the different mouse models studied has allowed us to identify someavenues. Interesting for each disease independently but also highlighted some common signatures between the different studies.
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Submitted on : Monday, July 25, 2022 - 5:06:10 PM
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Iman Haddad. Caractérisation protéomique du matrisome des maladies des petits vaisseaux cérébraux par spectrométrie de masse. Chimie analytique. Université Paris sciences et lettres, 2020. Français. ⟨NNT : 2020UPSLS026⟩. ⟨tel-03738070⟩

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