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

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
Source :
Biomedicines, Vol 9, Iss 11, p 1518 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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 Light was investigated in dissecting AAA induced by angiotensin II (AngII) in the Apolipoprotein E-deficient (Apoe−/−) mice. Studies in aortic human (ah) vascular smooth muscle cells (VSMC) to study potential translation to human pathology were also performed. AngII-treated Apoe−/−Light−/− mice displayed increased abdominal aorta maximum diameter and AAA severity compared with Apoe−/− mice. Notably, reduced smooth muscle α-actin+ area and Acta2 and Col1a1 gene expression were observed in AAA from Apoe−/−Light−/− mice, suggesting a loss of VSMC contractile phenotype compared with controls. Decreased Opn and augmented Sox9 expression, which are associated with detrimental and non-contractile osteochondrogenic VSMC phenotypes, were also seen in AngII-treated Apoe−/−Light−/− mouse AAA. Consistent with a role of LIGHT preserving VSMC contractile characteristics, LIGHT-treatment of ahVSMCs diminished the expression of SOX9 and of the pluripotency marker CKIT. 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.

Details

Language :
English
ISSN :
22279059
Volume :
9
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.f74087f9be3e4f8498c9c7cce0dd4d90
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines9111518