The Role of Focal Adhesion Kinase in Flow Induced Signaling

Petzold, Tobias, Department of Microbiology, University of Virginia
Parsons, Thomas, Department of Microbiology, University of Virginia

Atherosclerosis is a chronic vascular inflammatory disease that develops in areas of disturbed flow like artery bifurcations and branch points. The transcription factor NF-kB is activated in atherosclerotic lesions and stimulates E-selectin, ICAM-1 and VCAM-1 expression, which mediate leukocyte recruitment. NF-kB activation by flow is downstream of integrin activation. Focal adhesion kinase (FAK) is a critical mediator of integrin signaling. To test FAK's role in flowinduced NF-kB activation, I isolated mouse aortic endothelial cells from conditional FAK knockout mice. Cre adenovirus caused complete loss of FAK from the conditional cells. Shear stress activated NF-kB in WT but not FAK-/- endothelial cells, whereas Erk activation was similar in both cell types. While, reactive oxygen species (ROS) are critical mediators of flow induced NF-kB activation production their production was unaffected in FAK-/- cells, arguing the FAK might be involved in a distinct pathway of NF-kB activation by flow.

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MA (Master of Arts)
Atherosclerosis, vascular inflammation, artery bifurcations
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