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Pulsatile laminar flow keeps the vascular endothelium in a quiescent state via the regulation of a Kruppel‐Like Factor 2 pathway
Author(s) -
Young Angela Chienhsin,
Li YiShuan Julie,
Shyy John J,
Chien Shu
Publication year - 2008
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.22.1_supplement.1155.10
Subject(s) - klf2 , microbiology and biotechnology , chemistry , ampk , protein kinase a , biology , transcription factor , kinase , biochemistry , gene
Vascular endothelial cells (ECs) along the straight part of the arterial tree are generally spared from atherosclerosis by maintaining a quiescent phenotype, thus being protected from EC activation and leukocyte adhesion. The objective of this study is to elucidate the role of Krüppel‐Like Factor 2 (KLF2), a transcription factor that inhibits cell proliferation, in the athero‐protective action of pulsatile laminar flow (PS), which has high shear stress and a large net forward direction that mimics the athero‐protective flow pattern in the straight vessels. We have previously shown that PS inhibits EC proliferation and can induce KLF2. In the current study, using BrdU incorporation and immunostaining, we showed that 24‐hr PS caused a significant reduction of cell proliferation rate to 2% in comparison to 20% in static cells. Knocking down KLF2 (to ∼50%) with siRNA reversed the PS‐reduction of cell proliferation rate up to 11%. These results indicate that the anti‐proliferative action of PS is mediated by KLF2. To elucidate the signaling upstream to KLF2, we found that blocking AMP‐activated protein kinase (AMPK) prevented PS‐induced KLF2 expression. Thus, PS causes an activation of KLF2 through AMPK. These results provide a mechanistic explanation for the athero‐protective action of PS flow via the AMPK‐KLF2 pathway. (This work is supported by Grant HL064382 and UC San Diego Cardiovascular Scholarship Award)