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Expression and role of lumican in acute aortic dissection: A human and mouse study

INTRODUCTION: Aortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model. METHODS: LUM expression patterns were analyzed...

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Autores principales: Chen, Shao-Wei, Chou, Shing-Hsien, Tung, Ying-Chang, Hsiao, Fu-Chih, Ho, Chien-Te, Chan, Yi-Hsin, Wu, Victor Chien-Chia, Chou, An-Hsun, Hsu, Ming-En, Lin, Pyng-Jing, Kao, Winston W. Y., Chu, Pao-Hsien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312931/
https://www.ncbi.nlm.nih.gov/pubmed/34310653
http://dx.doi.org/10.1371/journal.pone.0255238
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author Chen, Shao-Wei
Chou, Shing-Hsien
Tung, Ying-Chang
Hsiao, Fu-Chih
Ho, Chien-Te
Chan, Yi-Hsin
Wu, Victor Chien-Chia
Chou, An-Hsun
Hsu, Ming-En
Lin, Pyng-Jing
Kao, Winston W. Y.
Chu, Pao-Hsien
author_facet Chen, Shao-Wei
Chou, Shing-Hsien
Tung, Ying-Chang
Hsiao, Fu-Chih
Ho, Chien-Te
Chan, Yi-Hsin
Wu, Victor Chien-Chia
Chou, An-Hsun
Hsu, Ming-En
Lin, Pyng-Jing
Kao, Winston W. Y.
Chu, Pao-Hsien
author_sort Chen, Shao-Wei
collection PubMed
description INTRODUCTION: Aortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model. METHODS: LUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum(−/−)) mice were challenged with β-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN–Ang II–challenged wildtype (WT) mice. Tgf-β/Smad2, Mmps, Lum, and Nox expression patterns were examined. RESULTS: LUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum(−/−) AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum(−/−) AD mice compared with the WT AD mice. The BAPN–Ang II–challenged WT and Lum(−/−) AD mice had higher Tgf-β, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II–challenged WT in comparison to the unchallenged WT mice. CONCLUSION: LUM expression was altered in patients with AD display increased s-LUM in blood, and Lum(−/−) mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes.
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spelling pubmed-83129312021-07-31 Expression and role of lumican in acute aortic dissection: A human and mouse study Chen, Shao-Wei Chou, Shing-Hsien Tung, Ying-Chang Hsiao, Fu-Chih Ho, Chien-Te Chan, Yi-Hsin Wu, Victor Chien-Chia Chou, An-Hsun Hsu, Ming-En Lin, Pyng-Jing Kao, Winston W. Y. Chu, Pao-Hsien PLoS One Research Article INTRODUCTION: Aortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model. METHODS: LUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum(−/−)) mice were challenged with β-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN–Ang II–challenged wildtype (WT) mice. Tgf-β/Smad2, Mmps, Lum, and Nox expression patterns were examined. RESULTS: LUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum(−/−) AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum(−/−) AD mice compared with the WT AD mice. The BAPN–Ang II–challenged WT and Lum(−/−) AD mice had higher Tgf-β, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II–challenged WT in comparison to the unchallenged WT mice. CONCLUSION: LUM expression was altered in patients with AD display increased s-LUM in blood, and Lum(−/−) mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes. Public Library of Science 2021-07-26 /pmc/articles/PMC8312931/ /pubmed/34310653 http://dx.doi.org/10.1371/journal.pone.0255238 Text en © 2021 Chen et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chen, Shao-Wei
Chou, Shing-Hsien
Tung, Ying-Chang
Hsiao, Fu-Chih
Ho, Chien-Te
Chan, Yi-Hsin
Wu, Victor Chien-Chia
Chou, An-Hsun
Hsu, Ming-En
Lin, Pyng-Jing
Kao, Winston W. Y.
Chu, Pao-Hsien
Expression and role of lumican in acute aortic dissection: A human and mouse study
title Expression and role of lumican in acute aortic dissection: A human and mouse study
title_full Expression and role of lumican in acute aortic dissection: A human and mouse study
title_fullStr Expression and role of lumican in acute aortic dissection: A human and mouse study
title_full_unstemmed Expression and role of lumican in acute aortic dissection: A human and mouse study
title_short Expression and role of lumican in acute aortic dissection: A human and mouse study
title_sort expression and role of lumican in acute aortic dissection: a human and mouse study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312931/
https://www.ncbi.nlm.nih.gov/pubmed/34310653
http://dx.doi.org/10.1371/journal.pone.0255238
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