Vigliotti, Chiara (2018) “Role of Autophagy in the regulation of Angiogenesis in Stroke”. [Tesi di dottorato]

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Angiogenesis is the extension of new blood vessels from the preexisting vessels. This mechanism occurs in pathological conditions of the CNS such as stroke, brain tumors or neurotrauma. After ischemic stroke and brain injury, angiogenesis tries to restore tissue perfusion by developing new vessels. VEGF was traditionally regarded as the primary factor activated in the angiogenic reparation and it has been proposed to in the therapy of neurodegenerative diseases. Unfortunately, the VEGF is not a good drug candidate for its pharmacokinetic limitations and its capacity to permeabilize the cerebral endothelium causing brain leakage. Due to the increasing evidences from literature showing an involvement of autophagy in new vessels formation it has been verified whether autophagy could have a role in blood vessel formation in a pathological condition where the failure to supply blood to suffering brain is crucial, the ischemic stroke. There are different conditions in the brain that promote autophagy such as oxygen deprivation with activation of angiogenesis. To test our working hypothesis, in vitro experiments were performed in order to evaluate whether autophagy could be involved in vitro tubulogenesis by modulating the autophagic cascade. In these experiments, brain endothelial cells (bEND5) VEGF independents and forming a capillary-like network when plated on Matrigel, were used. Hereafter, it has been evaluated if the experimental hypothesis tested in vitro experiments could be confirmed also in vivo experiments in rodents thus allowing us to verify whether autophagy could be considered a mechanism involved in angiogenesis and therefore it could be proposed as a target for the therapy of stroke.

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