Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
Soon-Gook Hong, … , Xiaofeng Yang, Joon-Young Park
Soon-Gook Hong, … , Xiaofeng Yang, Joon-Young Park
Published September 22, 2022
Citation Information: JCI Insight. 2022;7(18):e159286. https://doi.org/10.1172/jci.insight.159286.
View: Text | PDF
Research Article Vascular biology

Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells

  • Text
  • PDF
Abstract

Endothelial mitochondria play a pivotal role in maintaining endothelial cell (EC) homeostasis through constantly altering their size, shape, and intracellular localization. Studies show that the disruption of the basal mitochondrial network in EC, forming excess fragmented mitochondria, implicates cardiovascular disease. However, cellular consequences underlying the morphological changes in the endothelial mitochondria under distinctively different, but physiologically occurring, flow patterns (i.e., unidirectional flow [UF] versus disturbed flow [DF]) are largely unknown. The purpose of this study was to investigate the effect of different flow patterns on mitochondrial morphology and its implications in EC phenotypes. We show that mitochondrial fragmentation is increased at DF-exposed vessel regions, where elongated mitochondria are predominant in the endothelium of UF-exposed regions. DF increased dynamin-related protein 1 (Drp1), mitochondrial reactive oxygen species (mtROS), hypoxia-inducible factor 1, glycolysis, and EC activation. Inhibition of Drp1 significantly attenuated these phenotypes. Carotid artery ligation and microfluidics experiments further validate that the significant induction of mitochondrial fragmentation was associated with EC activation in a Drp1-dependent manner. Contrarily, UF in vitro or voluntary exercise in vivo significantly decreased mitochondrial fragmentation and enhanced fatty acid uptake and OXPHOS. Our data suggest that flow patterns profoundly change mitochondrial fusion/fission events, and this change contributes to the determination of proinflammatory and metabolic states of ECs.

Authors

Soon-Gook Hong, Junchul Shin, Soo Young Choi, Jeffery C. Powers, Benjamin M. Meister, Jacqueline Sayoc, Jun Seok Son, Ryan Tierney, Fabio A. Recchia, Michael D. Brown, Xiaofeng Yang, Joon-Young Park

×

Graphical abstract

Options: View larger image (or click on image)

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts