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http://purl.uniprot.org/citations/16195476http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16195476http://www.w3.org/2000/01/rdf-schema#comment"

Background

Flow-induced regulation of endothelial NO synthase (eNOS) depends on integrin signaling and tyrosine kinase activation. Integrins cluster in focal adhesion complexes, where the extracellular matrix is connected to the cytoskeleton and where focal adhesion kinase (FAK) is located. FAK plays a central role in integrin signaling and Src activation. Accordingly, we hypothesized that FAK plays an important role in flow-induced dilation (FID).

Methods and results

To inactivate FAK-dependent signaling, anti-FAK, phosphospecific (Tyr397) antibody (FAKab), which binds against the FAK autophosphorylation site, was incorporated into endothelium of rat coronary arterioles using liposomal transfection. The responses to flow, acetylcholine (Ach), or the NO donor MAHAMANONOate (NOC-9) were observed before and after FAKab. In control and vehicles (denatured antibody or transfecting reagent alone), flow produced progressive dilation to a maximal value of 35% increase in diameter, which was inhibited by Nomega-nitro-L-arginine methyl ester (L-NAME). However, FAKab prevented FID (P<0.01 versus control). Combined treatment with FAKab and L-NAME did not produce inhibition greater than FAKab alone. FAKab did not blunt Ach- or NOC-9-induced dilation. Western analysis demonstrated that FAKab prevented flow-induced phosphorylation of FAK (pY397-FAK), Akt (pS473-Akt), and eNOS (pS1179-eNOS).

Conclusions

Our study demonstrates the pivotal role of FAK in NO-mediated FID. Inhibition of FAK signaling with FAKab impaired FID and phosphorylation of Akt and eNOS. Our data suggest that the activation of FAK is central to the mechanotransduction of FID via regulation of activation of Akt and eNOS."xsd:string
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http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/author"Zhang C."xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/author"Saito S."xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/author"Rocic P."xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/author"Chilian W.M."xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/author"Koshida R."xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/author"Kiyooka T."xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/pages"2548-2553"xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/title"Role of focal adhesion kinase in flow-induced dilation of coronary arterioles."xsd:string
http://purl.uniprot.org/citations/16195476http://purl.uniprot.org/core/volume"25"xsd:string
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