摘要
背景:马方综合征(MFS)可导致升主动脉瘤(ATAA)。近期,转化生长因子(TGF-β)被认为参与ATAA形成过程。基质金属蛋白酶(MMP)及其内源性抑制因子(TIMP)间失衡也被证实促进动脉瘤形成。与非MFS患者相比较,MFS伴ATAA患者的MMP、TIMP以及TGF-β信号是否发生变化及变化程度如何仍属未知。
BACKGROUND -Marfan syndrome(MFS) is known to cause ascending thoracic aortic aneurysms(ATAAs). Transforming growth factor beta(TGF-β) has recently been implicated in this process. Imbalances between the matrix metalloproteinases(MMPs) and their endogenous inhibitors(TIMPs) have also been shown to contribute to aneurysm formation. Whether and to what degree MMP, TIMP, and TGF-βsignaling profiles are altered in ATAAs in MFS compared with non-MFS patients remains unknown. METHODS AND RESULTS -ATAA samples taken during aortic replacement from age-matched MFS(n=9) and non-MFS(n=18) patients were assessed for representative subtypes of all MMP classes, all 4 known TIMPs, and type 2 TGF-βreceptors(TGFBR2). Results were expressed as a percentage(mean±SEM) of reference control samples(100%; n=18) obtained from patients without ATAA. In MFS, decreased MMP-2(76±7%; P< 0.05 versus control), increased MMP-12(161±27%versus control; P< 0.05), and increased MT1-MMP(248±64%versus 91±21%non-MFS and control; P< 0.05) were observed. TIMP-3(74±23%) was reduced compared with control values(P< 0.05) and TIMP-2 was elevated(128±31%) compared with non-MFS(73±19%; P< 0.05). In non-MFS samples, MMP-1(70±16%), MMP-3(77±18%),MMP-8(75±11%), MMP-9(69±14%), and MMP-12(85±15%) were decreased compared with control(P< 0.05). TIMPs 1 to 3 were reduced in non-MFS compared with control values(P< 0.05). TGFBR2 were increased in MFS(193±32%)compared with non-MFS(95±16%) and controls(P< 0.05). CONCLUSIONS -A unique MMP and TIMP portfolio was observed in ATAAs from MFS compared with non-MFS patients. In addition, MFS samples showed evidence of increased TGF-βsignaling. These differences suggest disparate mechanisms of extracellular matrix remodeling between these 2 groups of patients.
