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Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells
Choi, Soo Young Powers, Jeffery C. Meister, Benjamin M. Sayoc, Jacqueline Son, Jun Seok Tierney, Ryan Recchia, Fabio A. Brown, Michael D.
Choi, Soo Young
Powers, Jeffery C.
Meister, Benjamin M.
Sayoc, Jacqueline
Son, Jun Seok
Tierney, Ryan
Recchia, Fabio A.
Brown, Michael D.
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Journal article
Date
2022-09-22
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Cardiovascular Sciences
Microbiology, Immunology and Inflammation
Biomedical Education and Data Science
Health and Rehabilitation Sciences
Microbiology, Immunology and Inflammation
Biomedical Education and Data Science
Health and Rehabilitation Sciences
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http://dx.doi.org/10.1172/jci.insight.159286
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.
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Flow pattern–dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells 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.
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American Society for Clinical Investigation
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JCI Insight, Vol. 7
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