Disturbed flow-induced FAK K152 SUMOylation initiates the formation of pro-inflammation positive feedback loop by inducing reactive oxygen species production in endothelial cells

Loka Reddy Velatooru, Rei J. Abe, Masaki Imanishi, Young Jin Gi, Kyung Ae Ko, Kyung Sun Heo, Keigi Fujiwara, Nhat Tu Le, Sivareddy Kotla

Research output: Contribution to journalArticlepeer-review

Abstract

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 redox-sensitive 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.

Original languageEnglish (US)
Pages (from-to)404-418
Number of pages15
JournalFree Radical Biology and Medicine
Volume177
DOIs
StatePublished - Dec 2021

Keywords

  • Disturbed flow
  • FAK
  • Reactive oxygen species
  • SUMOylation
  • p90RSK

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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