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 Light was investigated in dissecting AAA induced by ang...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | INCLIVA |
| Repositorio: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p16343 |
| Acceso en línea: | https://incliva.portalinvestigacion.com/publicaciones/16343 |
| Access Level: | acceso abierto |
| Palabra clave: | TNFSF14/LIGHT abdominal aortic aneurysm vascular smooth muscle cells |
| 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 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 a-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 ß receptor (LTßR) 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 LTßR-dependent manner. |
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