DIFFERENTIAL ACTIVATION OF NF-KAPPA-B IN HUMAN AORTIC ENDOTHELIAL-CELLS CONDITIONED TO SPECIFIC FLOW ENVIRONMENTS

Endothelial cell-monocyte interaction plays an important role in ather ogenesis. The expressions of some endothelial cell adhesion molecules involved in endothelial cell-monocyte interactions are regulated by tr anscription factor NF-kappa B. Because low shear stress has been known to influence endothelial monocyte adhesion, the differential activati on of NF-kappa B under different flow regimens across time (0.5-24 h) was investigated. Nuclear proteins from flow-conditioned human aortic endothelial cells (HAEC) were analyzed by electrophoretic mobility shi ft assay using [gamma-P-32]dATP-labeled NF-kappa B-specific oligonucle otide. Our results demonstrated that NF-kappa B activation was signifi cantly elevated in HAEC exposed to prolonged (>2 h) steady low shear ( 2 dyn/cm(2)) and pulsatile low shear (2 +/- 2 dyn/cm(2)) compared with HAEC exposed to high shear (16 dyn/cm(2)). In contrast, at 30 min, hi gh shear-exposed HAEC exhibited an early, transient increase in NF-kap pa B activity, relative to low shear-exposed cells, which reversed on continued exposure to high shear. Maximum activity in both low shear- and pulsatile low shear-conditioned HAEC was observed at 16 h compared with HAEC exposed to prolonged high shear. These results indicate tha t exposure of HAEC to prolonged low shear conditions is associated wit h significantly increased and prolonged NF-kappa B activity. This obse rvation might provide a mechanism to explain the increased monocyte ad hesion in atherosclerosis-prone arterial sites exposed to chronic low- shear flow patterns.