Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)

Abdominal aortic aneurysm (AAA), is a complex disorder characterized by vascular vessel wall remodeling. LIGHT (TNFSF14) is a proinflammatory cytokine associated with vascular disease. In the present study, the impact of genetic inactivation of <i>Light</i> was investigated in dissecting...

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Main Authors:	Andrea Herrero-Cervera, Carla Espinós-Estévez, Susana Martín-Vañó, Alida Taberner-Cortés, María Aguilar-Ballester, Ángela Vinué, Laura Piqueras, Sergio Martínez-Hervás, Herminia González-Navarro
Format:	article
Language:	EN
Published:	MDPI AG 2021
Subjects:	abdominal aortic aneurysm TNFSF14/LIGHT vascular smooth muscle cells Biology (General) QH301-705.5
Online Access:	https://doaj.org/article/f74087f9be3e4f8498c9c7cce0dd4d90
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spelling	oai:doaj.org-article:f74087f9be3e4f8498c9c7cce0dd4d902021-11-25T16:48:28ZDissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)10.3390/biomedicines91115182227-9059https://doaj.org/article/f74087f9be3e4f8498c9c7cce0dd4d902021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1518https://doaj.org/toc/2227-9059Abdominal aortic aneurysm (AAA), is a complex disorder characterized by vascular vessel wall remodeling. LIGHT (TNFSF14) is a proinflammatory cytokine associated with vascular disease. In the present study, the impact of genetic inactivation of <i>Light</i> was investigated in dissecting AAA induced by angiotensin II (AngII) in the Apolipoprotein E-deficient (<i>Apoe</i><sup>−/−</sup>) mice. Studies in aortic human (ah) vascular smooth muscle cells (VSMC) to study potential translation to human pathology were also performed. AngII-treated <i>Apoe</i><sup>−/−</sup><i>Light</i><sup>−/−</sup> mice displayed increased abdominal aorta maximum diameter and AAA severity compared with <i>Apoe</i><sup>−/−</sup> mice. Notably, reduced smooth muscle α-actin+ area and <i>Acta2</i> and <i>Col1a1</i> gene expression were observed in AAA from <i>Apoe</i><sup>−/−</sup><i>Light</i><sup>−/−</sup> mice, suggesting a loss of VSMC contractile phenotype compared with controls. Decreased <i>Opn</i> and augmented <i>Sox9</i> expression, which are associated with detrimental and non-contractile osteochondrogenic VSMC phenotypes, were also seen in AngII-treated <i>Apoe</i><sup>−/−</sup><i>Light</i><sup>−/−</sup> mouse AAA. Consistent with a role of LIGHT preserving VSMC contractile characteristics, LIGHT-treatment of ahVSMCs diminished the expression of <i>SOX9</i> and of the pluripotency marker <i>CKIT</i>. These effects were partly mediated through lymphotoxin β receptor (LTβR) as the silencing of its gene ablated LIGHT effects on ahVSMCs. These studies suggest a protective role of LIGHT through mechanisms that prevent VSMC trans-differentiation in an LTβR-dependent manner.Andrea Herrero-CerveraCarla Espinós-EstévezSusana Martín-VañóAlida Taberner-CortésMaría Aguilar-BallesterÁngela VinuéLaura PiquerasSergio Martínez-HervásHerminia González-NavarroMDPI AGarticleabdominal aortic aneurysmTNFSF14/LIGHTvascular smooth muscle cellsBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1518, p 1518 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	abdominal aortic aneurysm TNFSF14/LIGHT vascular smooth muscle cells Biology (General) QH301-705.5
spellingShingle	abdominal aortic aneurysm TNFSF14/LIGHT vascular smooth muscle cells Biology (General) QH301-705.5 Andrea Herrero-Cervera Carla Espinós-Estévez Susana Martín-Vañó Alida Taberner-Cortés María Aguilar-Ballester Ángela Vinué Laura Piqueras Sergio Martínez-Hervás Herminia González-Navarro Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)
description	Abdominal aortic aneurysm (AAA), is a complex disorder characterized by vascular vessel wall remodeling. LIGHT (TNFSF14) is a proinflammatory cytokine associated with vascular disease. In the present study, the impact of genetic inactivation of <i>Light</i> was investigated in dissecting AAA induced by angiotensin II (AngII) in the Apolipoprotein E-deficient (<i>Apoe</i><sup>−/−</sup>) mice. Studies in aortic human (ah) vascular smooth muscle cells (VSMC) to study potential translation to human pathology were also performed. AngII-treated <i>Apoe</i><sup>−/−</sup><i>Light</i><sup>−/−</sup> mice displayed increased abdominal aorta maximum diameter and AAA severity compared with <i>Apoe</i><sup>−/−</sup> mice. Notably, reduced smooth muscle α-actin+ area and <i>Acta2</i> and <i>Col1a1</i> gene expression were observed in AAA from <i>Apoe</i><sup>−/−</sup><i>Light</i><sup>−/−</sup> mice, suggesting a loss of VSMC contractile phenotype compared with controls. Decreased <i>Opn</i> and augmented <i>Sox9</i> expression, which are associated with detrimental and non-contractile osteochondrogenic VSMC phenotypes, were also seen in AngII-treated <i>Apoe</i><sup>−/−</sup><i>Light</i><sup>−/−</sup> mouse AAA. Consistent with a role of LIGHT preserving VSMC contractile characteristics, LIGHT-treatment of ahVSMCs diminished the expression of <i>SOX9</i> and of the pluripotency marker <i>CKIT</i>. These effects were partly mediated through lymphotoxin β receptor (LTβR) as the silencing of its gene ablated LIGHT effects on ahVSMCs. These studies suggest a protective role of LIGHT through mechanisms that prevent VSMC trans-differentiation in an LTβR-dependent manner.
format	article
author	Andrea Herrero-Cervera Carla Espinós-Estévez Susana Martín-Vañó Alida Taberner-Cortés María Aguilar-Ballester Ángela Vinué Laura Piqueras Sergio Martínez-Hervás Herminia González-Navarro
author_facet	Andrea Herrero-Cervera Carla Espinós-Estévez Susana Martín-Vañó Alida Taberner-Cortés María Aguilar-Ballester Ángela Vinué Laura Piqueras Sergio Martínez-Hervás Herminia González-Navarro
author_sort	Andrea Herrero-Cervera
title	Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)
title_short	Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)
title_full	Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)
title_fullStr	Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)
title_full_unstemmed	Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)
title_sort	dissecting abdominal aortic aneurysm is aggravated by genetic inactivation of light (tnfsf14)
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f74087f9be3e4f8498c9c7cce0dd4d90
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Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14)

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