Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics

Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previouslyshowed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosisdevelopment in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion andtransendothelial migration (TEM) and to decipher the underlying mechanisms of these actions.Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5–1 μM) for 3 h prior to theiractivation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelialmigration assays were conducted under static condition and shear stress that mimics blood flow. Wefurther investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays.Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migrationin both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeabilityand the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expressionof 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed thatcurcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested bymolecular docking analysis.Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulationof the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier