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FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment
Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628247/ https://www.ncbi.nlm.nih.gov/pubmed/37932296 http://dx.doi.org/10.1038/s41467-023-42690-9 |
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author | Sun, Zongchao Yang, Likun Kiram, Abdukahar Yang, Jing Yang, Zhuangzhuang Xiao, Liwei Yin, Yujing Liu, Jing Mao, Yan Zhou, Danxia Yu, Hao Zhou, Zheng Xu, Dengqiu Jia, Yuhuan Ding, Chenyun Guo, Qiqi Wang, Hongwei Li, Yan Wang, Li Fu, Tingting Hu, Shijun Gan, Zhenji |
author_facet | Sun, Zongchao Yang, Likun Kiram, Abdukahar Yang, Jing Yang, Zhuangzhuang Xiao, Liwei Yin, Yujing Liu, Jing Mao, Yan Zhou, Danxia Yu, Hao Zhou, Zheng Xu, Dengqiu Jia, Yuhuan Ding, Chenyun Guo, Qiqi Wang, Hongwei Li, Yan Wang, Li Fu, Tingting Hu, Shijun Gan, Zhenji |
author_sort | Sun, Zongchao |
collection | PubMed |
description | Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a process pivotal for muscle revascularization during ischemia. Muscle FNIP1 expression is down-regulated by exercise. Genetic overexpression of FNIP1 in myofiber causes limited angiogenesis in mice, whereas its myofiber-specific ablation markedly promotes the formation of functional blood vessels. Interestingly, the increased muscle angiogenesis is independent of AMPK but due to enhanced macrophage recruitment in FNIP1-depleted muscles. Mechanistically, myofiber FNIP1 deficiency induces PGC-1α to activate chemokine gene transcription, thereby driving macrophage recruitment and muscle angiogenesis program. Furthermore, in a mouse hindlimb ischemia model of peripheral artery disease, the loss of myofiber FNIP1 significantly improved the recovery of blood flow. Thus, these results reveal a pivotal role of FNIP1 as a negative regulator of functional angiogenesis in muscle, offering insight into potential therapeutic strategies for ischemic diseases. |
format | Online Article Text |
id | pubmed-10628247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106282472023-11-08 FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment Sun, Zongchao Yang, Likun Kiram, Abdukahar Yang, Jing Yang, Zhuangzhuang Xiao, Liwei Yin, Yujing Liu, Jing Mao, Yan Zhou, Danxia Yu, Hao Zhou, Zheng Xu, Dengqiu Jia, Yuhuan Ding, Chenyun Guo, Qiqi Wang, Hongwei Li, Yan Wang, Li Fu, Tingting Hu, Shijun Gan, Zhenji Nat Commun Article Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a process pivotal for muscle revascularization during ischemia. Muscle FNIP1 expression is down-regulated by exercise. Genetic overexpression of FNIP1 in myofiber causes limited angiogenesis in mice, whereas its myofiber-specific ablation markedly promotes the formation of functional blood vessels. Interestingly, the increased muscle angiogenesis is independent of AMPK but due to enhanced macrophage recruitment in FNIP1-depleted muscles. Mechanistically, myofiber FNIP1 deficiency induces PGC-1α to activate chemokine gene transcription, thereby driving macrophage recruitment and muscle angiogenesis program. Furthermore, in a mouse hindlimb ischemia model of peripheral artery disease, the loss of myofiber FNIP1 significantly improved the recovery of blood flow. Thus, these results reveal a pivotal role of FNIP1 as a negative regulator of functional angiogenesis in muscle, offering insight into potential therapeutic strategies for ischemic diseases. Nature Publishing Group UK 2023-11-06 /pmc/articles/PMC10628247/ /pubmed/37932296 http://dx.doi.org/10.1038/s41467-023-42690-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sun, Zongchao Yang, Likun Kiram, Abdukahar Yang, Jing Yang, Zhuangzhuang Xiao, Liwei Yin, Yujing Liu, Jing Mao, Yan Zhou, Danxia Yu, Hao Zhou, Zheng Xu, Dengqiu Jia, Yuhuan Ding, Chenyun Guo, Qiqi Wang, Hongwei Li, Yan Wang, Li Fu, Tingting Hu, Shijun Gan, Zhenji FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment |
title | FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment |
title_full | FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment |
title_fullStr | FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment |
title_full_unstemmed | FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment |
title_short | FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment |
title_sort | fnip1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628247/ https://www.ncbi.nlm.nih.gov/pubmed/37932296 http://dx.doi.org/10.1038/s41467-023-42690-9 |
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