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Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14).
- Source :
-
Biomedicines [Biomedicines] 2021 Oct 22; Vol. 9 (11). Date of Electronic Publication: 2021 Oct 22. - Publication Year :
- 2021
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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