| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1927829 | Biochemical and Biophysical Research Communications | 2016 | 7 Pages |
•Arp2/3 complex is increased under atherosclerotic conditions.•Arp2/3 complex is necessary for ox-LDL-induced endothelial dysfunction.•LOX-1 mediates the effects of ox-LDL on Arp2/3 complex by activating Rac-1.•Arp2/3 complex mediates the progression of atherosclerosis in vivo.
Oxidized low-density lipoproteins (ox-LDL) play a critical role in endothelial injury including cytoskeleton reorganization, which is closely related to actin-related protein 2/3 (Arp2/3) complex. The aim of this study was to investigate the role of Arp2/3 complex in ox-LDL-induced endothelial dysfunction. In this study, we found that Arp2 and Arp3 expression was increased under atherosclerotic conditions both in ApoE−/− mice and in ox-LDL-stimulated human coronary artery endothelial cells (HCAECs). Arp2/3 complex inhibitor CK666 significantly reduced ox-LDL-induced ROS generation and cytoskeleton reorganization, and increased NO release in HCAECs. Pretreatment with LOX-1- but not CD36-blocking antibody markedly decreased ox-LDL-induced Arp2 and Arp3 expression. Moreover, Rac-1 siRNA remarkably suppressed ox-LDL-stimulated Arp2 and Arp3 expression. Additionally, CK666 reduced endothelial nitric oxide synthase (eNOS) expression and atherosclerotic lesions in ApoE−/− mice. Collectively, ox-LDL induces endothelial dysfunction by activating LOX-1/Rac-1 signaling and upregulating Arp2/3 complex expression.
