科研之友
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摘要
The lethality of acute aortic dissection is well recognized Successful treatment and prevention of aortic dissection is going to be dependent upon an improved understanding of the molecular and physiologic events which predispose to dissection development and propagation In this review, we will focus on the elastic fiber, one of the critical elements of the aortic wall matrix Mechanical or functional failure of the elastin in the wall of the aorta likely predisposes to dissection as well as the post-dissection aortic degeneration with aneurysm formation Insight into the role of the elastin and the elastic fiber in aortic dissection has recently been accelerated by research into the molecular mechanisms associated with hereditary propensity for aortic dissection, such as Marfan syndrome These studies have implicated both structural and metabolic contributions of alterations in the scaffolding proteins in matrix elastic fibers In particular, increased transforming growth factor-beta (TGF-beta) activity may play a prominent role in predisposing the aortic wall to dissection The events which predispose to post-dissection aortic degeneration are somewhat less well defined However, the loss of the structural integrity of the remaining elastic fibers leaves the wall weaker and prone to dilatation and rupture It appears likely that the upregulation of several potent proteases, particularly those of the matrix metalloproteinase (MMP) family such as MMP-9, are participating in the sub sequent matrix damage Novel medical treatments based on this pathologic data have been proposed and in some cases have made it to clinical trials The ongoing study evaluating whether therapeutic inhibition of TGF-beta may be useful in reducing the risk of aortic dissection in patients at high risk represents one promising new strategy in the treatment of this deadly disease
- 出版日期2010-10
