S. Mohan et al., DIFFERENTIAL ACTIVATION OF NF-KAPPA-B IN HUMAN AORTIC ENDOTHELIAL-CELLS CONDITIONED TO SPECIFIC FLOW ENVIRONMENTS, American journal of physiology. Cell physiology, 42(2), 1997, pp. 572-578
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.