Intermittent hypoxia (IH), the major feature of obstructive sleep apnea syndrome (OSAS), induc-es atherosclerosis and elastic fiber alterations. VE-cadherin cleavage is increased in OSAS pa-tients and in an IH-cellular model. It is mediated by HIF-1 and Src-tyr-kinases pathways and re-sults in endothelial hyperpermeability. Our aim was to determine whether blocking VE-cadherin cleavage in vivo could be an efficient strategy to inhibit deleterious IH-induced vascular remodeling, elastic fiber defects and atherogenesis. VE-cadherin regulation, aortic re-modeling and atherosclerosis were studied in IH-exposed C57Bl/6J or Ap-oE-/- mice treated or not with Src-tyr-kinases inhibitors (Saracat-inib/Pazopanib) or a HIF-1 inhibitor (Acriflavine). Human aortic endothelial cells were exposed to IH and treated with the same inhibitors. LDL and the monocytes transendothelium passage were measured. In vitro, IH increased transendothelium LDL and monocytes passage, and the tested inhibitors prevented these effects. In mice, IH decreased VE-cadherin expression and in-creased plasmatic sVE level, intima-media thickness, elastic fiber alterations and atherosclerosis, while the inhibitors prevented these in vivo effects. In vivo inhibition of HIF-1 and Src tyr ki-nase pathways were associated with the prevention of IH-induced elastic fiber/lamella degrada-tion and atherogenesis, which suggests that VE-cadherin could be an important target to limit atherogenesis and progression of arterial stiffness in OSAS.