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Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) limits therapeutic revascularization. Neuropeptide Y (NPY), co-stored and co-released with the sympathetic nervous system, is involved in this process, but its exact role and underlying mechanisms remain to be fully understood. Th...

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Autores principales: Peng, Song, Wu, Wei-qiang, Li, Lin-yu, Shi, Yan-chuan, Lin, Shu, Song, Zhi-yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164319/
https://www.ncbi.nlm.nih.gov/pubmed/37149580
http://dx.doi.org/10.1186/s12872-023-03267-y
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author Peng, Song
Wu, Wei-qiang
Li, Lin-yu
Shi, Yan-chuan
Lin, Shu
Song, Zhi-yuan
author_facet Peng, Song
Wu, Wei-qiang
Li, Lin-yu
Shi, Yan-chuan
Lin, Shu
Song, Zhi-yuan
author_sort Peng, Song
collection PubMed
description BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) limits therapeutic revascularization. Neuropeptide Y (NPY), co-stored and co-released with the sympathetic nervous system, is involved in this process, but its exact role and underlying mechanisms remain to be fully understood. This study aimed to investigate the role of NPY in neointima formation after vascular injury. METHODS: Using the left carotid arteries of wild-type (WT, NPY-intact) and NPY-deficient (NPY(−/−)) mice, ferric chloride-mediated carotid artery injury induced neointima formation. Three weeks after injury, the left injured carotid artery and contralateral uninjured carotid artery were collected for histological analysis and immunohistochemical staining. RT-qPCR was used to detect the mRNA expression of several key inflammatory markers and cell adhesion molecules in vascular samples. Raw264.7 cells were treated with NPY, lipopolysaccharide (LPS), and lipopolysaccharide-free, respectively, and RT-qPCR was used to detect the expression of these inflammatory mediators. RESULTS: Compared with WT mice, NPY(−/−) mice had significantly reduced neointimal formation three weeks after injury. Mechanistically, immunohistochemical analysis showed there were fewer macrophages and more vascular smooth muscle cells in the neointima of NPY(−/−) mice. Moreover, the mRNA expression of key inflammatory markers such as interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and intercellular adhesion molecule-1 (ICAM-1) was significantly lower in the injured carotid arteries of NPY(−/−) mice, compared to that in the injured carotid arteries of WT mice. In RAW264.7 macrophages, NPY significantly promoted TGF-β1 mRNA expression under unactivated but not LPS-stimulated condition. CONCLUSIONS: Deletion of NPY attenuated neointima formation after artery injury, at least partly, through reducing the local inflammatory response, suggesting that NPY pathway may provide new insights into the mechanism of restenosis.
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spelling pubmed-101643192023-05-08 Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice Peng, Song Wu, Wei-qiang Li, Lin-yu Shi, Yan-chuan Lin, Shu Song, Zhi-yuan BMC Cardiovasc Disord Research BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) limits therapeutic revascularization. Neuropeptide Y (NPY), co-stored and co-released with the sympathetic nervous system, is involved in this process, but its exact role and underlying mechanisms remain to be fully understood. This study aimed to investigate the role of NPY in neointima formation after vascular injury. METHODS: Using the left carotid arteries of wild-type (WT, NPY-intact) and NPY-deficient (NPY(−/−)) mice, ferric chloride-mediated carotid artery injury induced neointima formation. Three weeks after injury, the left injured carotid artery and contralateral uninjured carotid artery were collected for histological analysis and immunohistochemical staining. RT-qPCR was used to detect the mRNA expression of several key inflammatory markers and cell adhesion molecules in vascular samples. Raw264.7 cells were treated with NPY, lipopolysaccharide (LPS), and lipopolysaccharide-free, respectively, and RT-qPCR was used to detect the expression of these inflammatory mediators. RESULTS: Compared with WT mice, NPY(−/−) mice had significantly reduced neointimal formation three weeks after injury. Mechanistically, immunohistochemical analysis showed there were fewer macrophages and more vascular smooth muscle cells in the neointima of NPY(−/−) mice. Moreover, the mRNA expression of key inflammatory markers such as interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and intercellular adhesion molecule-1 (ICAM-1) was significantly lower in the injured carotid arteries of NPY(−/−) mice, compared to that in the injured carotid arteries of WT mice. In RAW264.7 macrophages, NPY significantly promoted TGF-β1 mRNA expression under unactivated but not LPS-stimulated condition. CONCLUSIONS: Deletion of NPY attenuated neointima formation after artery injury, at least partly, through reducing the local inflammatory response, suggesting that NPY pathway may provide new insights into the mechanism of restenosis. BioMed Central 2023-05-06 /pmc/articles/PMC10164319/ /pubmed/37149580 http://dx.doi.org/10.1186/s12872-023-03267-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Peng, Song
Wu, Wei-qiang
Li, Lin-yu
Shi, Yan-chuan
Lin, Shu
Song, Zhi-yuan
Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice
title Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice
title_full Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice
title_fullStr Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice
title_full_unstemmed Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice
title_short Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice
title_sort deficiency of neuropeptide y attenuates neointima formation after vascular injury in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164319/
https://www.ncbi.nlm.nih.gov/pubmed/37149580
http://dx.doi.org/10.1186/s12872-023-03267-y
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