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

Authors :
Herrero-Cervera A
Espinós-Estévez C
Martín-Vañó S
Taberner-Cortés A
Aguilar-Ballester M
Vinué Á
Piqueras L
Martínez-Hervás S
González-Navarro H
Source :
Biomedicines [Biomedicines] 2021 Oct 22; Vol. 9 (11). Date of Electronic Publication: 2021 Oct 22.
Publication Year :
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 <superscript>-/-</superscript> ) mice. Studies in aortic human (ah) vascular smooth muscle cells (VSMC) to study potential translation to human pathology were also performed. AngII-treated Apoe <superscript>-/-</superscript> Light <superscript>-/-</superscript> mice displayed increased abdominal aorta maximum diameter and AAA severity compared with Apoe <superscript>-/-</superscript> mice. Notably, reduced smooth muscle α-actin+ area and Acta2 and Col1a1 gene expression were observed in AAA from Apoe <superscript>-/-</superscript> Light <superscript>-/-</superscript> 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 <superscript>-/-</superscript> Light <superscript>-/-</superscript> 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 :
2227-9059
Volume :
9
Issue :
11
Database :
MEDLINE
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
34829747
Full Text :
https://doi.org/10.3390/biomedicines9111518