En conclusion, les résultats présentés dans ce mémoire démontrent le rôle du facteur de transcription HIF-1 dans les maladies vasculaires à remodelage. Les travaux clarifient les rôles de HIF-1 dans la prolifération des cellules musculaires lisses vasculaires stimulées par divers agonistes, dans leur résistance à l'apoptose via la régulation de l'hexokinase II et dans leur métabolisme glycolytique. De plus, une voie importante dans la régulation de l'expression de HIF-la et dans la prolifération a été clarifiée. Aussi, les travaux ont montré que l'inhibition de HIF-1 dans un modèle animal de maladies vasculaires à remodelage permettait de diminuer la formation de la néointima suite à une angioplastie artérielle. Cette étude renforce donc le fait que HIF-1 semble une cible thérapeutique intéressante dans le traitement des MVR.
Les travaux de ce mémoire ont permis aussi de renforcer les connaissances du rôle de la cytokine TNF dans les maladies vasculaires à remodelage. En effet, nous avons démontré une présence plus élevée chez les patients atteints de MVR ainsi que dans un modèle animal de MVR. Nous avons montré qu'en diminuant la présence de TNF libre dans le sang, nous diminuons la formation de remodelage chez un modèle animal post- angioplastie par entre autres la diminution d'activation de HIF-1. Cette autre étude renforce encore une fois le rôle de HIF-1 dans ces pathologies.
5.2 Perspectives
Il serait intéressant d'étudier le rôle de l'axe HIF-la/PPARy dans la régulation du métabolisme lipidique des MVR ainsi que leur interaction et les voies de signalisation qui amène leur activation. De plus, il serait intéressant d'étudier les voies de signalisation de l'isoforme HIF-3a faisant partie de la famille des HIF. Celui-ci est connu pour avoir une activité inhibitrice sur HIF-la, ce qui pourrait éventuellement devenir une nouvelle cible thérapeutique dans le traitement des MVR.
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