Document Detail

Aortic dilatation with bicuspid aortic valves: cusp fusion correlates to matrix metalloproteinases and inhibitors.
MedLine Citation:
PMID:  22206960     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Congenital bicuspid aortic valves (BAVs) result from fusion of 2 valve cusps, resulting in left-noncoronary (L-N), right-left (R-L), and right-noncoronary (R-N) morphologic presentations. BAVs predispose to ascending thoracic aortic aneurysms (ATAAs). This study hypothesized that ATAAs with each BAV morphologic group possess unique signatures of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of metalloproteinases (TIMPs).
METHODS: Ascending thoracic aortic aneurysm tissue from 46 patients with BAVs was examined for MMP/TIMP abundance, and global MMP activity was compared with normal aortic specimens (n=15). Proteolytic balance was calculated as the ratio of MMP abundance to a composite TIMP score. Results were stratified by valve morphologic group (L-N [n=6], R-L [n=31], and R-N [n=9]).
RESULTS: The BAV specimens (p<0.05 versus normal aorta, 100%) displayed elevated global MMP activity (273%±63%), MMP-9 (263%±47%), and decreased MMP-7 (56%±10%), MMP-8 (58%±11%), TIMP-1 (63%±7%), and TIMP-4 (38%±3%). The R-L group showed increased global MMP activity (286%±89%) and MMP-9 (267%±55%) with reduced MMP-7 (45%±7%), MMP-8 (68%±15%), TIMP-1 (58%±7%), and TIMP-4 (35%±3%). The L-N group showed elevated global MMP activity (284%±71%) and decreased MMP-8 (37%±17%) and TIMP-4 (48%±14) activity. In the R-N group, MMP-7 (46%±13%) and MMP-8 (36%±17%) and TIMP-1 (59%±10%) and TIMP-4 (42%±5%) were decreased. The R-L group demonstrated an increased proteolytic balance for MMP-1, MMP-9, and MMP-12 relative to L-N and R-N.
CONCLUSIONS: Each BAV morphologic group possesses a unique signature of MMPs and TIMPs. MMP/TIMP score ratios suggest that the R-L group may be more aggressive, justifying earlier surgical intervention.
John S Ikonomidis; Jean Marie Ruddy; Stewart M Benton; Jazmine Arroyo; Theresa A Brinsa; Robert E Stroud; Ahmed Zeeshan; Joseph E Bavaria; Joseph H Gorman; Robert C Gorman; Francis G Spinale; Jeffrey A Jones
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-28
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  93     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-24     Completed Date:  2012-03-20     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  457-63     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Aorta / abnormalities*,  enzymology,  pathology,  surgery
Aortic Aneurysm, Thoracic / epidemiology,  etiology
Aortic Valve / abnormalities*,  enzymology,  pathology,  surgery
Blood Vessel Prosthesis Implantation
Dilatation, Pathologic / enzymology
Disease Susceptibility
Elastic Tissue / pathology
Extracellular Matrix Proteins / analysis
Matrix Metalloproteinases / analysis*
Middle Aged
Tissue Inhibitor of Metalloproteinases / analysis*
Grant Support
R01 AG036954/AG/NIA NIH HHS; R01 AG036954-01A1/AG/NIA NIH HHS; R01 HL102121/HL/NHLBI NIH HHS; R01 HL102121-01A1/HL/NHLBI NIH HHS; R01 HL103723/HL/NHLBI NIH HHS; R21 HL089170/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Extracellular Matrix Proteins; 0/Tissue Inhibitor of Metalloproteinases; EC 3.4.24.-/Matrix Metalloproteinases
Comment In:
Ann Thorac Surg. 2012 Feb;93(2):463-4   [PMID:  22269713 ]

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