Low shear stress exacerbates atherosclerosis by inducing the generation of neutrophil extracellular traps via Piezo1-mediated mechanosensation
Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved..
BACKGROUND AND AIMS: Atherosclerosis is a chronic lipid-driven inflammatory disease largely influenced by hemodynamics. Neutrophil extracellular trap (NET)-mediated inflammation plays an important role in atherosclerosis. However, little is known about the relationship between low shear stress (LSS) and NET generation, as well as the underlying mechanism.
METHODS: We induced LSS by partial ligation of the left carotid artery in high-fat diet-fed male ApoE-/- mice. To further validate the direct relationship between LSS and NET formation invitro, differentiated human promyelocytic leukemia HL-60 cells and bone marrow-derived neutrophils were suspended in fluid flow under normal or low shear stress using a parallel-plate flow chamber system.
RESULTS: Four weeks after surgery, ligated carotid arteries had more lipid deposition, larger plaque area, and increased NET formation than unligated arteries. Inhibition of NETosis could significantly reduce plaque formation in ApoE-/- mice. Invitro, LSS could promote NET generation directly through downregulation of Piezo1, a mechanosensitive ion channel. Downregulation of Piezol could activate neutrophils and promote NETosis in static conditions. Conversely, Yoda1-evoked activation of Piezo1 attenuated LSS-induced NETosis. Mechanistically, downregulation of Piezo1 resulted in decreased Ca2+ influx and increased histone deacetylase 2 (HDAC2), which increased reactive oxygen species levels and led to NETosis. LSS-induced NET generation also promoted apoptosis and adherence of endothelial cells.
CONCLUSION: LSS directly promotes NETosis through the Piezo1-HDAC2 axis in atherosclerosis progression. This study uncovers the essential role of Piezo1-mediated mechanical signaling in NET generation and plaque formation, which provides a promising therapeutic strategy for atherosclerosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:391 |
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| Enthalten in: |
Atherosclerosis - 391(2024) vom: 27. Apr., Seite 117473 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Ying [VerfasserIn] |
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| Links: |
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| Themen: |
Apolipoproteins E |
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| Anmerkungen: |
Date Completed 12.04.2024 Date Revised 24.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.atherosclerosis.2024.117473 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369026918 |
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| 100 | 1 | |a Zhu, Ying |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Low shear stress exacerbates atherosclerosis by inducing the generation of neutrophil extracellular traps via Piezo1-mediated mechanosensation |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 24.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND AND AIMS: Atherosclerosis is a chronic lipid-driven inflammatory disease largely influenced by hemodynamics. Neutrophil extracellular trap (NET)-mediated inflammation plays an important role in atherosclerosis. However, little is known about the relationship between low shear stress (LSS) and NET generation, as well as the underlying mechanism | ||
| 520 | |a METHODS: We induced LSS by partial ligation of the left carotid artery in high-fat diet-fed male ApoE-/- mice. To further validate the direct relationship between LSS and NET formation invitro, differentiated human promyelocytic leukemia HL-60 cells and bone marrow-derived neutrophils were suspended in fluid flow under normal or low shear stress using a parallel-plate flow chamber system | ||
| 520 | |a RESULTS: Four weeks after surgery, ligated carotid arteries had more lipid deposition, larger plaque area, and increased NET formation than unligated arteries. Inhibition of NETosis could significantly reduce plaque formation in ApoE-/- mice. Invitro, LSS could promote NET generation directly through downregulation of Piezo1, a mechanosensitive ion channel. Downregulation of Piezol could activate neutrophils and promote NETosis in static conditions. Conversely, Yoda1-evoked activation of Piezo1 attenuated LSS-induced NETosis. Mechanistically, downregulation of Piezo1 resulted in decreased Ca2+ influx and increased histone deacetylase 2 (HDAC2), which increased reactive oxygen species levels and led to NETosis. LSS-induced NET generation also promoted apoptosis and adherence of endothelial cells | ||
| 520 | |a CONCLUSION: LSS directly promotes NETosis through the Piezo1-HDAC2 axis in atherosclerosis progression. This study uncovers the essential role of Piezo1-mediated mechanical signaling in NET generation and plaque formation, which provides a promising therapeutic strategy for atherosclerosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Atherosclerosis | |
| 650 | 4 | |a Low shear stress | |
| 650 | 4 | |a Neutrophil extracellular traps | |
| 650 | 4 | |a Piezo1 | |
| 650 | 7 | |a Apolipoproteins E |2 NLM | |
| 650 | 7 | |a Ion Channels |2 NLM | |
| 650 | 7 | |a Lipids |2 NLM | |
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| 650 | 7 | |a PIEZO1 protein, human |2 NLM | |
| 700 | 1 | |a Wang, Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zining |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Liu |e verfasserin |4 aut | |
| 700 | 1 | |a Niu, Ruyan |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Zixin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Chong |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yijie |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Wei |e verfasserin |4 aut | |
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