Important role of the angiotensin II pathway in producing matrix metalloproteinase-9 in human thoracic aortic aneurysms.
J Surg Res
; 183(1): 472-7, 2013 Jul.
Article
en En
| MEDLINE
| ID: mdl-23295196
ABSTRACT
BACKGROUND:
The precise pathologic mechanisms underlying human thoracic aortic aneurysms (TAAs) remain uncertain, except that matrix metalloproteinase-9 (MMP-9) is considered a key enzyme for the degradation of extracellular matrix in aneurysm walls. The aim of this study was to elucidate the significance of the angiotensin II (AngII) pathway to MMP-9 production in human TAA walls. METHODS ANDRESULTS:
We examined the activation of Smad2, a common downstream molecule of AngII and transforming growth factor ß (TGF-ß) pathways, and the expression of MMP-9 in human nonsyndromic TAA walls. We observed significant increases in Smad2 activation and MMP-9 expression, associated with disruption of elastic lamellae. Using human TAA walls in ex vivo culture, we investigated whether AngII and/or TGF-ß pathways are essential for MMP-9 production. Unexpectedly, TGF-ß receptor inhibitor had no effect on MMP-9 production. We used PD98059, an inhibitor of extracellular signal-regulated kinase (ERK) activation, and demonstrated that PD98059 dramatically reduced MMP-9 production with attenuation of Smad2 activation. Moreover, exogenous AngII resulted in increases in Smad2 activation and MMP-9 production, in an ERK-dependent manner.CONCLUSION:
Our findings indicate that the AngII/ERK pathway has an important role in the production of MMP-9 in human nonsyndromic TAA walls.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Angiotensina II
/
Factor de Crecimiento Transformador beta
/
Aneurisma de la Aorta Torácica
/
Metaloproteinasa 9 de la Matriz
/
Proteína Smad2
Límite:
Humans
Idioma:
En
Revista:
J Surg Res
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón