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

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 c...

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Autores principales: Hong, Soon-Gook, Shin, Junchul, Choi, Soo Young, Powers, Jeffery C., Meister, Benjamin M., Sayoc, Jacqueline, Son, Jun Seok, Tierney, Ryan, Recchia, Fabio A., Brown, Michael D., Yang, Xiaofeng, Park, Joon-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9514384/
https://www.ncbi.nlm.nih.gov/pubmed/36134656
http://dx.doi.org/10.1172/jci.insight.159286
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author Hong, Soon-Gook
Shin, Junchul
Choi, Soo Young
Powers, Jeffery C.
Meister, Benjamin M.
Sayoc, Jacqueline
Son, Jun Seok
Tierney, Ryan
Recchia, Fabio A.
Brown, Michael D.
Yang, Xiaofeng
Park, Joon-Young
author_facet Hong, Soon-Gook
Shin, Junchul
Choi, Soo Young
Powers, Jeffery C.
Meister, Benjamin M.
Sayoc, Jacqueline
Son, Jun Seok
Tierney, Ryan
Recchia, Fabio A.
Brown, Michael D.
Yang, Xiaofeng
Park, Joon-Young
author_sort Hong, Soon-Gook
collection PubMed
description 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.
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spelling pubmed-95143842022-09-30 Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells Hong, Soon-Gook Shin, Junchul Choi, Soo Young Powers, Jeffery C. Meister, Benjamin M. Sayoc, Jacqueline Son, Jun Seok Tierney, Ryan Recchia, Fabio A. Brown, Michael D. Yang, Xiaofeng Park, Joon-Young JCI Insight Research Article 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. American Society for Clinical Investigation 2022-09-22 /pmc/articles/PMC9514384/ /pubmed/36134656 http://dx.doi.org/10.1172/jci.insight.159286 Text en © 2022 Hong et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Hong, Soon-Gook
Shin, Junchul
Choi, Soo Young
Powers, Jeffery C.
Meister, Benjamin M.
Sayoc, Jacqueline
Son, Jun Seok
Tierney, Ryan
Recchia, Fabio A.
Brown, Michael D.
Yang, Xiaofeng
Park, Joon-Young
Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
title Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
title_full Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
title_fullStr Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
title_full_unstemmed Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
title_short Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
title_sort flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9514384/
https://www.ncbi.nlm.nih.gov/pubmed/36134656
http://dx.doi.org/10.1172/jci.insight.159286
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