کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6254432 | 1288428 | 2013 | 6 صفحه PDF | دانلود رایگان |
BackgroundThe 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 and resultsWe examined the activation of Smad2, a common downstream molecule of AngII and transforming growth factor β (TGF-β) 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-β pathways are essential for MMP-9 production. Unexpectedly, TGF-β 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.ConclusionOur findings indicate that the AngII/ERK pathway has an important role in the production of MMP-9 in human nonsyndromic TAA walls.
Journal: Journal of Surgical Research - Volume 183, Issue 1, July 2013, Pages 472-477