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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| Autores principales: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/f74087f9be3e4f8498c9c7cce0dd4d90 |
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| Sumario: | 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. |
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