Altogether, the results from this in vitro study demonstrate the protective effect of Roflumilast against irradiation-induced endothelial dysfunctions (endothelial barrier disruption, apoptosis, adherens junction and actin cytoskeleton alterations) in a primary microvascular endothelial cell model, suggesting that this PDE4 inhibitor may alleviate irradiation-induced organ damages in case of exposure to high doses of radiation. The gene discussed is PDE4A; the disease is endothelial dysfunction.