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Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice
While neutrophil extracellular traps (NETs) have previously been linked to some diabetes-associated complications, such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not been studied. Diabetic Akita mice were crossed with either Elane(−/−) or Pad4(−/−) mic...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599623/ https://www.ncbi.nlm.nih.gov/pubmed/37878711 http://dx.doi.org/10.1126/sciadv.adj1019 |
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author | Liu, Chao Yalavarthi, Srilakshmi Tambralli, Ajay Zeng, Lixia Rysenga, Christine E. Alizadeh, Nikoo Hudgins, Lucas Liang, Wenying NaveenKumar, Somanathapura K. Shi, Hui Shelef, Miriam A. Atkins, Kevin B. Pennathur, Subramaniam Knight, Jason S. |
author_facet | Liu, Chao Yalavarthi, Srilakshmi Tambralli, Ajay Zeng, Lixia Rysenga, Christine E. Alizadeh, Nikoo Hudgins, Lucas Liang, Wenying NaveenKumar, Somanathapura K. Shi, Hui Shelef, Miriam A. Atkins, Kevin B. Pennathur, Subramaniam Knight, Jason S. |
author_sort | Liu, Chao |
collection | PubMed |
description | While neutrophil extracellular traps (NETs) have previously been linked to some diabetes-associated complications, such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not been studied. Diabetic Akita mice were crossed with either Elane(−/−) or Pad4(−/−) mice to generate NET-deficient diabetic mice. By 24 weeks of age, Akita aortae showed markedly impaired relaxation in response to acetylcholine, indicative of vascular dysfunction. Both Akita-Elane(−/−) mice and Akita-Pad4(−/−) mice had reduced levels of circulating NETs and improved acetylcholine-mediated aortic relaxation. Compared with wild-type aortae, the thromboxane metabolite TXB(2) was roughly 10-fold higher in both intact and endothelium-denuded aortae of Akita mice. In contrast, Akita-Elane(−/−) and Akita-Pad4(−/−) aortae had TXB(2) levels similar to wild type. In summary, inhibition of NETosis by two independent strategies prevented the development of vascular dysfunction in diabetic Akita mice. Thromboxane was up-regulated in the vessel walls of NETosis-competent diabetic mice, suggesting a role for neutrophils in driving the production of this vasoconstrictive and atherogenic prostanoid. |
format | Online Article Text |
id | pubmed-10599623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105996232023-10-26 Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice Liu, Chao Yalavarthi, Srilakshmi Tambralli, Ajay Zeng, Lixia Rysenga, Christine E. Alizadeh, Nikoo Hudgins, Lucas Liang, Wenying NaveenKumar, Somanathapura K. Shi, Hui Shelef, Miriam A. Atkins, Kevin B. Pennathur, Subramaniam Knight, Jason S. Sci Adv Biomedicine and Life Sciences While neutrophil extracellular traps (NETs) have previously been linked to some diabetes-associated complications, such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not been studied. Diabetic Akita mice were crossed with either Elane(−/−) or Pad4(−/−) mice to generate NET-deficient diabetic mice. By 24 weeks of age, Akita aortae showed markedly impaired relaxation in response to acetylcholine, indicative of vascular dysfunction. Both Akita-Elane(−/−) mice and Akita-Pad4(−/−) mice had reduced levels of circulating NETs and improved acetylcholine-mediated aortic relaxation. Compared with wild-type aortae, the thromboxane metabolite TXB(2) was roughly 10-fold higher in both intact and endothelium-denuded aortae of Akita mice. In contrast, Akita-Elane(−/−) and Akita-Pad4(−/−) aortae had TXB(2) levels similar to wild type. In summary, inhibition of NETosis by two independent strategies prevented the development of vascular dysfunction in diabetic Akita mice. Thromboxane was up-regulated in the vessel walls of NETosis-competent diabetic mice, suggesting a role for neutrophils in driving the production of this vasoconstrictive and atherogenic prostanoid. American Association for the Advancement of Science 2023-10-25 /pmc/articles/PMC10599623/ /pubmed/37878711 http://dx.doi.org/10.1126/sciadv.adj1019 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Liu, Chao Yalavarthi, Srilakshmi Tambralli, Ajay Zeng, Lixia Rysenga, Christine E. Alizadeh, Nikoo Hudgins, Lucas Liang, Wenying NaveenKumar, Somanathapura K. Shi, Hui Shelef, Miriam A. Atkins, Kevin B. Pennathur, Subramaniam Knight, Jason S. Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice |
title | Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice |
title_full | Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice |
title_fullStr | Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice |
title_full_unstemmed | Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice |
title_short | Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice |
title_sort | inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599623/ https://www.ncbi.nlm.nih.gov/pubmed/37878711 http://dx.doi.org/10.1126/sciadv.adj1019 |
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