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NFkB Regulation by Different Flow Patterns
Author(s) -
Flores Leona,
Chien Shu
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb91-c
Subject(s) - pulsatile flow , inflammation , nf κb , microbiology and biotechnology , mediator , chemistry , nfkb1 , transcription factor , medicine , endocrinology , biophysics , biology , biochemistry , gene
Fluid mechanical shear stress influences the structure and function of vascular endothelial cells (ECs) and has emerged as a significant factor in atherogenesis. Pulsatile flow exerts an anti‐inflammatory effect, whereas oscillatory flow (found at arterial branch points) stimulates downstream inflammatory events. The transcription factor NFκB plays a central role in inflammatory processes. NFκB activation affects multiple cells and tissues implicated in atherosclerosis, including EC, and may be an important mediator of the inflammatory response in ECs. The objective of this study is to establish the expression profile of the NFκB pathway under different flow patterns and its role in mediating and modulating the downstream EC inflammatory events. Our studies have shown that pulsatile flow (PS, 12±4 dyn/cm 2 ) induced transient IkBα degradation, returning to the basal level by 4 hr. In contrast, oscillatory flow (OS, 0.5±4 dyn/cm 2 ) induced sustained IkBα degradation, lasting for at least 24 hr. The differential effects of PS and OS on IkBα degradation led to corresponding differences in NFκB translocation, which was transient with PS and sustained with OS. These results indicate that different flow patterns cause different temporal regulation of NFκB signaling, which may in turn lead to the differential regulation of EC inflammatory responses. NIH grant HL064382 (SC); NHLBI HL064382‐06S (LF).