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PAR‐1 is a novel mechano‐sensor transducing laminar flow‐mediated endothelial signaling
Author(s) -
Kim Suji,
Nam Daehwan,
Han Junghwa,
Woo ChangHoon
Publication year - 2013
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.27.1_supplement.1031.6
Subject(s) - microbiology and biotechnology , laminar flow , signal transduction , g protein coupled receptor , chemistry , receptor , biology , biochemistry , physics , thermodynamics
Laminar blood flow acts mainly on vascular endothelial cells(ECs) which modulates atheroprotective functions. ECs express laminar flow‐mediating molecules of the mechano‐sensor including G proteins, integrin, and growth factor receptor. However, flow‐mediated signaling pathway of G protein and GPCR is not well established. Recent studies have indicated that PAR‐1 Known as GPCR which involves cytoprotective and anti‐inflammatory responses in endothelial cells. Here, we addressed whether the PAR‐1 is involved by laminar flow‐mediated atheroprotective signaling. In present study, depletion of PAR‐1 with siRNA against human PAR‐1 inhibited flow‐mediated KLF2‐and Nrf2‐dependent gene expression in ECs. In addition, confocal analysis showed that PAR‐1 was internalized into early endosome in response to laminar flow suggesting that PAR‐1 is activated by laminar blood flow. We identified HDAC5 as a downstream target molecule of PAR‐1. Furthermore depletion of PAR‐1 reversed the flow‐mediated anti‐inflammatory response for TNFa‐induced VCAM‐1 expression and monocyte adhesiveness. Taken together, these results provide that flow‐induced PAR‐1 activation exerts atheroprotective signaling pathway in ECs.