期刊
CIRCULATION
卷 114, 期 -, 页码 I365-I370出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.105.000810
关键词
aneurysm; aorta; Marfan; MMP; TIMP
资金
- NHLBI NIH HHS [R01 HL 059165-07, R01 HL075488-01] Funding Source: Medline
Background-Marfan syndrome (MFS) is known to cause ascending thoracic aortic aneurysms (ATAAs). Transforming growth factor beta (TGF-beta) 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-beta signaling 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-beta receptors (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 ( 3 +/- 19%; P < 0.05). In non-MFS samples, MMP-1 ( 70 +/- 16%), MMP-3 ( 7 +/- 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-beta signaling. These differences suggest disparate mechanisms of extracellular matrix remodeling between these 2 groups of patients.
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