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Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation
OBJECTIVES: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. METHODS AND RESUL...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8852280/ https://www.ncbi.nlm.nih.gov/pubmed/35187100 http://dx.doi.org/10.3389/fcvm.2021.761591 |
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author | Namiguchi, Kenji Sakaue, Tomohisa Okazaki, Mikio Kanno, Kaho Komoda, Yuhei Shikata, Fumiaki Kurata, Mie Ota, Noritaka Kubota, Yoshiaki Kurobe, Hirotsugu Nishimura, Takashi Masumoto, Junya Higashiyama, Shigeki Izutani, Hironori |
author_facet | Namiguchi, Kenji Sakaue, Tomohisa Okazaki, Mikio Kanno, Kaho Komoda, Yuhei Shikata, Fumiaki Kurata, Mie Ota, Noritaka Kubota, Yoshiaki Kurobe, Hirotsugu Nishimura, Takashi Masumoto, Junya Higashiyama, Shigeki Izutani, Hironori |
author_sort | Namiguchi, Kenji |
collection | PubMed |
description | OBJECTIVES: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. METHODS AND RESULTS: We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-β/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-β/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity. CONCLUSIONS: Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues. |
format | Online Article Text |
id | pubmed-8852280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88522802022-02-18 Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation Namiguchi, Kenji Sakaue, Tomohisa Okazaki, Mikio Kanno, Kaho Komoda, Yuhei Shikata, Fumiaki Kurata, Mie Ota, Noritaka Kubota, Yoshiaki Kurobe, Hirotsugu Nishimura, Takashi Masumoto, Junya Higashiyama, Shigeki Izutani, Hironori Front Cardiovasc Med Cardiovascular Medicine OBJECTIVES: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. METHODS AND RESULTS: We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-β/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-β/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity. CONCLUSIONS: Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8852280/ /pubmed/35187100 http://dx.doi.org/10.3389/fcvm.2021.761591 Text en Copyright © 2022 Namiguchi, Sakaue, Okazaki, Kanno, Komoda, Shikata, Kurata, Ota, Kubota, Kurobe, Nishimura, Masumoto, Higashiyama and Izutani. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Namiguchi, Kenji Sakaue, Tomohisa Okazaki, Mikio Kanno, Kaho Komoda, Yuhei Shikata, Fumiaki Kurata, Mie Ota, Noritaka Kubota, Yoshiaki Kurobe, Hirotsugu Nishimura, Takashi Masumoto, Junya Higashiyama, Shigeki Izutani, Hironori Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation |
title | Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation |
title_full | Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation |
title_fullStr | Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation |
title_full_unstemmed | Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation |
title_short | Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation |
title_sort | unique angiogenesis from cardiac arterioles during pericardial adhesion formation |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8852280/ https://www.ncbi.nlm.nih.gov/pubmed/35187100 http://dx.doi.org/10.3389/fcvm.2021.761591 |
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