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FAK and endothelial cell isometric tension
Author(s) -
Miede Kimberly,
Goeckeler Zoe,
Wysolmerski Robert
Publication year - 2010
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.24.1_supplement.lb423
Subject(s) - focal adhesion , extracellular matrix , microbiology and biotechnology , chemistry , isometric exercise , endothelial stem cell , myosin , cell migration , extracellular , cell , biology , signal transduction , biochemistry , physiology , in vitro
The vascular system is lined by a continuous sheet of endothelial cells (EC) that form a semi‐permeable barrier. Inflammatory stimuli trigger EC contraction and intracellular gap formation, resulting in an increase in vascular permeability. Activation of EC contractile activity and/or alterations in cell–matrix adhesion most likely cause inter‐endothelial cell gap formation. Cell‐matrix adhesion occurs through multi‐protein complexes called focal adhesions (FA). FA tether the cells contractile machinery (actin/myosin) to extracellular matrix proteins forming the structural link necessary for isometric tension generation. To investigate the role of FA in EC contraction, focal adhesion kinase (FAK) was ablated. We propose FAK is essential for isometric tension generation and is necessary for assembly and organization of the EC contractile machinery. Infection of EC with a FAK‐shRNA caused a 90% reduction in endogenous levels of FAK protein as well as a 50% reduction in EC FA compared to vector controls. Up‐regulation of Pyk2 was not detected. FAK knockdown reduces basal EC tension and inhibits LPA induced isometric tension generation. Loss of FAK alters nonmuscle myosin II distribution suggesting a role for FAK in myosin II regulation. These data implicate FAK in the regulation of EC isometric tension. Supported by NIH grants T32‐HL090610, HL‐45788, RR‐16440.