Portal de investigación
Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14).
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Herrero-Cervera, A
- Espinos-Estevez, C
- Vinue, A
Grupos y Plataformas de I+D+i
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 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.
Datos de la publicación
- ISSN/ISSNe:
- 2227-9059, 2227-9059
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 34829747
Biomedicines MDPI AG
Citas Recibidas en Web of Science: 5
Documentos
Filiaciones
Keywords
- TNFSF14/LIGHT; abdominal aortic aneurysm; vascular smooth muscle cells
Financiación
Proyectos y Estudios Clínicos
Role of the inflammatory processes in metabolic diseases and associated complications. Papel de los procesos inflamatorios en las enfermedades metabólicas y sus complicaciones asociadas.
Investigador Principal: HERMINIA GONZÁLEZ NAVARRO
PI19/00169 . INSTITUTO SALUD CARLOS III . 2020
CDEI-04/20-B BENT-T HERMINIA GONZALEZ (2019/198) CONTRATO
Investigador Principal: HERMINIA GONZÁLEZ NAVARRO
2019/198C . CONSELLERIA DE SANIDAD
Cita
Herrero A,Espinos C,Martin S,0000-0003-4974-7327,Aguilar M,Vinue A,Piqueras L,Martinez S,Gonzalez H. Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14). Biomedicines. 2021. 9. (11):1518. IF:4,757. (2).
Dissecting Abdominal Aortic Aneurysm Is Aggravated by Genetic Inactivation of LIGHT (TNFSF14). Herrero A, Espinos C, Martin S, 0000-0003-4974-7327, Aguilar M, Vinue A, Piqueras L et al. Biomedicines. 2021 octubre 22. 9 (11):DOI:10.3390/biomedicines9111518. PMID:34829747.
