Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 177, Issue -, Pages 404-418Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2021.09.023
Keywords
Disturbed flow; Reactive oxygen species; p90RSK; FAK; SUMOylation
Funding
- National Institutes of Health [HL-134740]
Ask authors/readers for more resources
Activation of focal adhesion kinase (FAK) in endothelial cells plays a crucial role in vascular diseases such as atherosclerosis. The study shows that disturbed flow (D-flow) induces endothelial activation and senescence through the upregulation of FAK SUMOylation, and mutating this site significantly inhibits these processes.
Focal adhesion kinase (FAK) activation plays a crucial role in vascular diseases. In endothelial cells, FAK activation is involved in the activation of pro-inflammatory signaling and the progression of atherosclerosis. Disturbed flow (D-flow) induces endothelial activation and senescence, but the exact role of FAK in D-flow induced endothelial activation and senescence remains unclear. The objective of this study is to investigate the role of FAK SUMOylation in D-flow-induced endothelial activation and senescence. The results showed that D flow induced reactive oxygen species (ROS) production via NADPH oxidase activation and activated a redoxsensitive kinase p90RSK, leading to FAK activation by upregulating FAK K152 SUMOylation and the subsequent Vav2 phosphorylation, which in turn formed a positive feedback loop by upregulating ROS production. This feedback loop played a crucial role in regulating endothelial activation and senescence. D-flow-induced endothelial activation and senescence were significantly inhibited by mutating a FAK SUMOylation site lysine152 to arginine. Collectively, we concluded that FAK K152 SUMOylation plays a key role in D-flow-induced endothelial activation and senescence by forming a positive feedback loop through ROS production.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available