Cardiovascular diseases are the number one cause of death globally. One key process central to disease development is dysfunction of the vascular endothelial barrier. Vascular endothelial cells normally maintain homeostasis by acting as a barrier, preventing the infiltration of circulating cells and proteins into tissues, but TNF-α-mediated breakdown of this barrier can cause vascular hyperpermeability, resulting in worsening disease. A new study examined a compound with the potential to protect against barrier dysfunction. S-1-propenylcysteine (S1PC) is a sulfur-containing constituent in aged garlic extract (AGE), a preparation with demonstrated anti-inflammatory and anti-atherosclerotic effects. Using TNF-α-stimulated human cell lines, researchers evaluated endothelial permeability, protein localization, and GTPase activity following treatment with AGE and S1PC. They found that AGE and S1PC reduced hyperpermeability caused by TNF-α. S1PC downregulated cytoskeletal remodeling following TNF-α stimulation and inhibited the activation of Rac and RhoA signaling. Future studies will focus on identifying the downstream target of S1PC, but these results suggest that AGE and S1PC may improve endothelial barrier disruption by protecting endothelial junctions, making them an ideal target for treating cardiovascular disease.