Oxidized low density lipoprotein induces endothelial-to-mesenchymal transition by stabilizing Snail in human aortic endothelial cells.

The endothelial-to-mesenchymal transition (EndMT) of endothelial cells contributes to the development of atherosclerosis. Oxidized low density lipoprotein (ox-LDL) is a highly risk factor for atherosclerosis. However, whether ox-LDL causes EndMT and the underlying mechanism are unclear. We report here that ox-LDL treatment is able to induce EndMT in human aortic endothelial cells (HAECs), and that the ox-LDL-induced EndMT is strictly dependent on the presence of its innate receptor, ox-LDL Receptor-1 (LOX-1). In addition, ox-LDL specifically upregulates EndMT transcriptional factor Snail, and knockdown of Snail completely attenuates ox-LDL-induced EndMT, indicating an essential role of Snail in mediating this effect. Mechanically, ox-LDL induces Snail stabilization by inhibiting its ubiquitination, which is in part attributed to inhibited GSK-3β activity. Hence, our findings suggest that inducing EndMT of aortic endothelial cells by ox-LDL might contribute to its detrimental role in promoting atherosclerosis development.