Document Detail

Temporal disparity in the induction of matrix metalloproteinases and tissue inhibitors of metalloproteinases after thoracic aortic aneurysm formation.
MedLine Citation:
PMID:  17000289     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: An important component of matrix remodeling during thoracic aortic aneurysm progression is the balance between matrix metalloproteinases and their endogenous inhibitors (tissue inhibitors of metalloproteinases). However, whether and to what degree matrix metalloproteinase/tissue inhibitor of metalloproteinases profiles change over time with an evolving thoracic aortic aneurysm remains unclear. METHODS: Descending thoracic aortic aneurysms were induced in mice (FVB strain, 15 minutes of 0.5 mol/L CaCl2 exposure) and followed for 24 hours, 72 hours, 1 week, 2 weeks, 4 weeks, or 8 weeks (each group, n = 13). Thoracic aortic aneurysm size was determined by means of video micrometry, and immunoblotting was used to measure aortic matrix metalloproteinase 2, 8, 9, and 12 and tissue inhibitor of metalloproteinases 1 and 4 levels (expressed as a percentage of control values, n = 13). RESULTS: Increased aortic diameter was detected by 72 hours and reached a maximal size at 4 weeks (135% +/- 4% increase from baseline, P < .05), which is consistent with thoracic aortic aneurysm progression. Active matrix metalloproteinase 8 (collagenase) levels increased at 72 hours (178% +/- 49%, P < .05 from control), and active matrix metalloproteinase 12 (elastase) levels increased by 24 hours (138% +/- 11%, P < .05), whereas active matrix metalloproteinase 2 levels increased at 72 hours and 1 week after thoracic aortic aneurysm induction (72 hours: 158% +/- 12%, 1 week: 162% +/- 19%; P < .05). At 1 week after thoracic aortic aneurysm induction, active matrix metalloproteinase 9 and 12 levels decrease (matrix metalloproteinase 9: 55% +/- 5%; matrix metalloproteinase 12: 63% +/- 5%; P < .05); however, matrix metalloproteinase 9 and 12 levels were increased from these values at 4 and 8 weeks (P < .05). Tissue inhibitor of metalloproteinases 1 levels were decreased at 1 week (52% +/- 15%, P < .05) and later returned to control values, whereas tissue inhibitor of metalloproteinases 4 levels increased at the late thoracic aortic aneurysm time points (4 weeks: 278% +/- 46%; 8 weeks: 213% +/- 40%; P < .05). CONCLUSIONS: These findings show 2 phases of matrix metalloproteinase abundance during murine thoracic aortic aneurysm formation. The late tissue inhibitor of metalloproteinases 4 increase might explain prevention of further aortic dilation past 4 weeks. Unique matrix metalloproteinase/tissue inhibitor of metalloproteinases temporal relationships occurred during the natural history of thoracic aortic aneurysm progression that might hold both diagnostic and therapeutic relevance.
John R Barbour; Robert E Stroud; Abigail S Lowry; Leslie L Clark; Allyson M Leone; Jeffery A Jones; Francis G Spinale; John S Ikonomidis
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  132     ISSN:  1097-685X     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-26     Completed Date:  2006-10-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  788-95     Citation Subset:  AIM; IM    
Cardiothoracic Surgical Research, Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
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MeSH Terms
Aortic Aneurysm, Thoracic / enzymology*
Enzyme Induction
Matrix Metalloproteinases / biosynthesis*
Time Factors
Tissue Inhibitor of Metalloproteinases / biosynthesis*
Grant Support
R01 HL059165-07/HL/NHLBI NIH HHS; R01 HL075488-01/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Tissue Inhibitor of Metalloproteinases; EC 3.4.24.-/Matrix Metalloproteinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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