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.