title: Low shear stress induced HMGB1 translocation and release via PECAM-1/PARP-1 pathway to induce inflammation response.
abstract: Low shear stress (LSS) plays a critical role in the site predilection of atherosclerosis through activation of cellular mechanosensors, such as platelet endothelial cell adhesion molecule 1 (PECAM-1). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that regulates the expression of various inflammatory cytokines. The nuclear enzyme high mobility group box 1 (HMGB1) can induce inflammation response by binding to toll-like receptor 4 (TLR4). In the present study, we aimed to investigate the role and mechanism of HMGB1 in LSS induced inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated by undisturbed shear stress (USS, 1 Pa) and LSS (0.4 Pa) in our experiments. Gene expression was inhibited by small interfering RNA (siRNA). ICAM-1 expression was regulated by LSS in a time dependent manner. LSS can induce HMGB1 translocation from nucleus to cytoplasm and release. Compared with the USS, LSS could increase the protein expression of PECAM-1 and PARP-1 as well as the secretion of TNF-α and IL-1β. LSS induced the translocation of HMGB1 from nucleus to cytoplasm. Inhibition of HGMB1 reduced LSS-induced inflammatory response. Inhibition of PARP-1 suppressed inflammatory response through inhibiting TLR4 expression and HMGB1 translocation. PECAM-1 inhibition reduced LSS-induced ICAM-1 expression, TNF-α and IL-1β secretion, and monocytes adhesion. LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway. PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression. Inhibition of PARP-1 may shed light on the treatment of HMGB1 involved inflammation during atherosclerosis.
authors: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Wei-dong
authors: WD
authors: Qin
authors: The Department of Cardiology, Yu Huang Ding Hospital, Yantai, Shandong, China.
authors: Shao-hua
authors: SH
authors: Mi
authors: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Chen
authors: C
authors: Li
authors: The Department of Radiology, Linyi People's Hospital, Linyi, Shandong, China.
authors: Gui-xia
authors: GX
authors: Wang
authors: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Jian-ning
authors: JN
authors: Zhang
authors: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Hao
authors: H
authors: Wang
authors: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Fan
authors: F
authors: Zhang
authors: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Yang
authors: Y
authors: Ma
authors: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Da-wei
authors: DW
authors: Wu
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors: Mingxiang
authors: M
authors: Zhang
mesh_terms: D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D021381:Protein Transport; D033081:Shear Strength; D015398:Signal Transduction; D013314:Stress, Mechanical; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D024243:HMGB1 Protein; D053583:Interleukin-1beta; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D011065:Poly(ADP-ribose) Polymerases