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 atherogenesis. The expressions of some endothelial cell adhesion molecules involved in endothelial cell-monocyte interactions are regulated by transcription factor NF-kappa B. Because low shear stress has been known to influence endothelial monocyte adhesion, the differential activation 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 shift assay using [gamma-32P]dATP-labeled NF-kappa B-specific oligonucleotide. Our results demonstrated that NF-kappa B activation was significantly elevated in HAEC exposed to prolonged (> 2 h) steady low shear (2 dyn/cm2) and pulsatile low shear (2 +/- 2 dyn/cm2) compared with HAEC exposed to high shear (16 dyn/cm2). In contrast, at 30 min, high shear-exposed HAEC exhibited an early, transient increase in NF-kappa 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 that exposure of HAEC to prolonged low shear conditions is associated with significantly increased and prolonged NF-kappa B activity. This observation might provide a mechanism to explain the increased monocyte adhesion in atherosclerosisprone arterial sites exposed to chronic low-shear flow patterns.
Mohan
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Department of Radiology, University of Texas Health Science Center, San Antonio 78284-7800, USA.
Mohan
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Sprague
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D000222:Adaptation, Physiological; D001011:Aorta / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D001783:Blood Flow Velocity; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007536:Isomerism; D016328:NF-kappa B / Q000378:metabolism*; D013314:Stress, Mechanical
D016328:NF-kappa B