title: ox-LDL induces endothelial dysfunction by promoting Arp2/3 complex expression.
abstract: 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.
authors.affiliation: Vascular Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215002, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Vascular Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215002, PR China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Vascular Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215002, PR China.
authors.forename: Liming
authors.initials: L
authors.lastname: Shen
authors.affiliation: Vascular Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215002, PR China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Vascular Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215002, PR China.
authors.forename: Zhixuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Vascular Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215002, PR China.
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Xu
authors.affiliation: Vascular Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215002, PR China. Electronic address: xianchenhuangnj@163.com.
authors.forename: Xianchen
authors.initials: X
authors.lastname: Huang
mesh_terms: D051377:Actin-Related Protein 2 / Q000378:metabolism*; D051378:Actin-Related Protein 3 / Q000378:metabolism*; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; C495929:Actr3 protein, mouse; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D020830:rac1 GTP-Binding Protein
keywords: Arp2/3; Endothelial dysfunction; LOX-1; Rac-1; ox-LDL