EGCG protects against oxLDL‐induced endothelial dysfunction by inhibiting LOX‐1‐mediated signaling

Abstract

Lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), originally identified as the major receptor for oxidized low‐density lipoprotein (oxLDL) in endothelial cells, plays a major role in the pathology of vascular diseases. In this study, we hypothesize that the most abundant polyphenolic compound in tea, epigallocatechin‐3‐gallate (EGCG), can down‐regulate parameters of endothelial dysfunction by modulating LOX‐1‐regulated cell signaling. In cultured human umbilical vein endothelial cells (HUVECs), exposure to oxLDL increased the expression of LOX‐1 at the RNA and protein levels. OxLDL rapidly activated the membrane translocation of Rac1 and p47phox and the subsequent induction of reactive oxygen species generation. It also increased p38MAPK phosphorylation and decreased the phosphorylation of Akt as well as nuclear translocation of NF‐κB. In addition, oxLDL diminished the expression of endothelial NO synthase, enhanced the expression of endothelin‐1 and adhesion molecules, and increased the adherence of monocytic THP‐1 cells to HUVECs. Pretreatment with EGCG, however, exerted significant cytoprotective effects. Results from this study may provide insight into a possible molecular mechanism by which EGCG suppresses oxLDL‐mediated vascular endothelial dysfunction. (This study was supported by grants from the National Science Council; NSC98‐2320‐B‐039‐020‐MY3).