IL-6: A Janus-like factor in abdominal aortic aneurysm disease.
Atherosclerosis
; 251: 139-146, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27318834
ABSTRACT
BACKGROUND AND AIMS:
An abdominal aortic aneurysm (AAA) is part of the atherosclerotic spectrum of diseases. The disease is hallmarked by a comprehensive localized inflammatory response with striking IL-6 hyperexpression. IL-6 is a multifaceted cytokine that, depending on the context, acts as a pro- or anti-inflammatory factor. In this study, we explore a putative role for IL-6 in AAA disease.METHODS:
ELISA's, Western blot analysis, real time PCR and array analysis were used to investigate IL-6 expression and signaling in aneurysm wall samples from patients undergoing elective AAA repair. A role for IL-6 in AAA disease was tested through IL-6 neutralization experiments (neutralizing antibody) in the elastase model of AAA disease.RESULTS:
We confirmed an extreme disparity in aortic wall IL-6 content between AAA and atherosclerotic disease (median [5th-95th percentile] aortic wall IL-6 content 281.6 [0.0-1820.8] (AAA) vs. 1.9 [0.0-37.8] µg/g protein (atherosclerotic aorta), (p < 0.001). Array analysis followed by pathway analysis showed that IL-6 hyper-expression is followed by increased IL-6 signaling (p < 0.000039), an observation confirmed by higher aneurysm wall pSTAT3 levels, and SOCS1 and SOCS3 mRNA expression, (p < 0.018). Remarkably, preventive IL-6 neutralization i.e. treatment started one day prior to the elastase-induction resulted in >40% 7-day mortality due to aortic rupture. In contrast, delayed IL-6 neutralization (i.e. neutralization started at day 4 after elastase induction) did not result in ruptures, and quenched AAA growth (p < 0.021).CONCLUSIONS:
AAA disease is characterized by increased IL-6 signaling. In the context of the elastase model of AAA disease, IL-6 appears a multi-faceted factor, protective upon acute injury, but negatively involved in the perpetuation of the disease process.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Interleucina-6
/
Aneurisma da Aorta Abdominal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Atherosclerosis
Ano de publicação:
2016
Tipo de documento:
Article