摘要
Aortic aneurysm(AA)is a common health problem with high mortality and no effective drugs.Transforming growth factor-β(TGF-β)superfamily members regulate various cellular processes,and TGF-βsignaling has key roles in development,tissue homeo-stasis,and diseases.Interest in the role of TGF-βsignaling in the pathogenesis of AAs has recently emerged,particularly since genetic studies demonstrated an association between gene mutations in components of TGF-βsignaling and AAs.However,paradoxical discoveries have implicated dysregulated TGF-βsignaling in aneurysm formation,complicating the precise functional role for TGF-βin aneurysm development and progression.Furthermore,interventions targeting towards TGF-βsignaling using losartan,which may represent a suitable therapeutic option for AAs,were subject to skepticism especially because of conflicting experimental results obtained from TGF-βantibody treatment without knowledge of the underlying mechanism.We propose a TGF-βaneurysm paradox,which would provide a good opportunity for the development of genetic mouse models of AA.These models would be used to clarify the mechanisms underlying TGF-βsignaling,which would translate into novel pharmacologic therapies based on the new molecular discoveries.
基金
supported by the grants from State Key Laboratory of Proteomics(No.SKLP-K200902)
Chinese Key Program for Drug Invention(No.2009ZX09501-027)
Chinese National Key Program on Basic Research(Nos.2005CB522506,2006CB943501 and 2006BAI23B01-3)
