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

<h4>Introduction</h4>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.<h4>Methods</h4>L...

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Autores principales:	Shao-Wei Chen, Shing-Hsien Chou, Ying-Chang Tung, Fu-Chih Hsiao, Chien-Te Ho, Yi-Hsin Chan, Victor Chien-Chia Wu, An-Hsun Chou, Ming-En Hsu, Pyng-Jing Lin, Winston W Y Kao, Pao-Hsien Chu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/61c06d75b5f04454b19582c337db1bd6
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spelling	oai:doaj.org-article:61c06d75b5f04454b19582c337db1bd62021-12-02T20:06:26ZExpression and role of lumican in acute aortic dissection: A human and mouse study.1932-620310.1371/journal.pone.0255238https://doaj.org/article/61c06d75b5f04454b19582c337db1bd62021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255238https://doaj.org/toc/1932-6203<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Shao-Wei ChenShing-Hsien ChouYing-Chang TungFu-Chih HsiaoChien-Te HoYi-Hsin ChanVictor Chien-Chia WuAn-Hsun ChouMing-En HsuPyng-Jing LinWinston W Y KaoPao-Hsien ChuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0255238 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shao-Wei Chen Shing-Hsien Chou Ying-Chang Tung Fu-Chih Hsiao Chien-Te Ho Yi-Hsin Chan Victor Chien-Chia Wu An-Hsun Chou Ming-En Hsu Pyng-Jing Lin Winston W Y Kao Pao-Hsien Chu Expression and role of lumican in acute aortic dissection: A human and mouse study.
description	<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
format	article
author	Shao-Wei Chen Shing-Hsien Chou Ying-Chang Tung Fu-Chih Hsiao Chien-Te Ho Yi-Hsin Chan Victor Chien-Chia Wu An-Hsun Chou Ming-En Hsu Pyng-Jing Lin Winston W Y Kao Pao-Hsien Chu
author_facet	Shao-Wei Chen Shing-Hsien Chou Ying-Chang Tung Fu-Chih Hsiao Chien-Te Ho Yi-Hsin Chan Victor Chien-Chia Wu An-Hsun Chou Ming-En Hsu Pyng-Jing Lin Winston W Y Kao Pao-Hsien Chu
author_sort	Shao-Wei Chen
title	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_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_sort	expression and role of lumican in acute aortic dissection: a human and mouse study.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/61c06d75b5f04454b19582c337db1bd6
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Expression and role of lumican in acute aortic dissection: A human and mouse study.

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