ID1 protein inhibitor depresses low-oscillating shear stress-mediated EndMT and atherosclerosis by Snail and Wnt/β-catenin signalling pathways

Abstract

Abstract The lateral pressure exerted by blood on the vessel wall, called low oscillating shear stress(OSS), destroys the endothelial cell barrier function through a process called EndMT and promotes the occurrence of atherosclerosis. The specific mechanism by which OSS regulates EndMT is still unclear. Inhibitor of differentiation 1 (ID1) is controlled by shear stress as an essential force-sensitive factor, and little is known about the effect of ID1 on EndMT in OSS-mediated atherosclerosis. This study investigated the impact of ID1 inhibitors on OSS-mediated EndMT in ApoE−/− mice and TGF-β1-induced human aortic endothelial cells (HAECs). First, we found that the expression of ID1 was down-regulated. At the same time, EndMT and plaque formation occurred in the ligated left common carotid artery (OSS) compared with the unligated right common carotid artery. Then, our results showed that the ID1 inhibitor AGX51 attenuated EndMT in atherosclerosis plaques in OSS mice. However, in vitro studies show that ID1 is upregulated in TGF-β1-treated HAECs and induces EndMT.sh-ID1 or AGX51 to inhibit the EndMT process and restore the migratory ability of endothelial cells. Furthermore, ID1 overexpression promoted the occurrence of EndMT.In addition, inhibition of ID1 may inhibit OSS-induced EndMT by regulating EndMT-specific transcription factors Snail and Wnt/β-catenin signalling pathway in vivo and in vitro by Immunohistochemistry and Western blot. These results suggest that ID1 inhibitors regulate the occurrence and development of low oscillating shear stress-mediated EndMT and atherosclerosis by Ctrlling Snail and Wnt/β-catenin signalling pathways.