In inflammatory vasculature, the leukocyte-released myeloperoxidase (MPO) is internalized by endothelial cells and this enzyme promotes endothelial dysfunction by catalytically producing strong oxidant, hypochlorous acid (HOCl). Herein, we developed epigallocatechin-3-gallate (EGCG, the main polyphenolic flavonoid found in green tea) as a novel endothelial-targeted MPO inhibitor. It was shown that culture of MPO and EGCG with vascular endothelial cells could result in their transport into the sub-endothelial space. EGCG significantly suppressed the consumption of enzyme's substrate H