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ABSTRACTPharmacological approaches aimed at increasing autophagic flux and genetically engineered mice with autophagy deficiency in the endothelium have demonstrated that autophagy exerts vessel protection against metabolic stresses and vascular aging. However, the identity of the specific cellular processes that autophagy controls in endothelial cells remained unclear. In this punctum, we discuss our recent findings on the multiple functions of autophagy in the endothelium. Particularly, we highlighted that autophagy controls flow-mediated vascular reactivity and remodeling. We have also focused on the role of autophagy machinery in regulating protein distribution within the cell and on the results demonstrating how autophagy modulates the cellular response to the microenvironment changes.Abbreviations: CXCL12: C-X-C motif chemokine ligand 12 EDN1: Endothelin 1 eNOS: endothelial Nitric Oxide Synthase FGF: Fibroblast Growth Factor NO: Nitric oxide VEGF: Vascular Endothelial Growth Factor VEGFR2: Vascular Endothelial Growth Factor Receptor 2