Document Detail


Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases.
MedLine Citation:
PMID:  15545515     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Elastin calcification is a widespread feature of vascular pathology, and circumstantial evidence exists for a correlation between elastin degradation and calcification. We hypothesized that matrix metalloproteinase (MMP)-mediated vascular remodeling plays a significant role in elastin calcification.
METHODS AND RESULTS: In the present studies, we determined that short-term periadventitial treatment of the rat abdominal aorta with low concentrations of calcium chloride (CaCl2) induced chronic degeneration and calcification of vascular elastic fibers in the absence of aneurysm formation and inflammatory reactions. Furthermore, the rate of progression of calcification depended on the application method and concentration of CaCl2 applied periarterially. Initial calcium deposits, associated mainly with elastic fibers, were persistently accompanied by elastin degradation, disorganization of aortic extracellular matrix, and moderate levels of vascular cell apoptosis. Application of aluminum ions (known inhibitors of elastin degradation) before the CaCl2-mediated injury significantly reduced elastin calcification and abolished both extracellular matrix degradation and apoptosis. We also found that MMP-knockout mice were resistant to CaCl2-mediated aortic injury and did not develop elastin degeneration and calcification.
CONCLUSIONS: Collectively, these data strongly indicate a correlation between MMP-mediated elastin degradation and vascular calcification.
Authors:
Dina M Basalyga; Dan T Simionescu; Wanfen Xiong; B Timothy Baxter; Barry C Starcher; Narendra R Vyavahare
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2004-11-15
Journal Detail:
Title:  Circulation     Volume:  110     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-30     Completed Date:  2005-06-13     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3480-7     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Abdominal / drug effects*,  metabolism,  pathology
Aortic Diseases / chemically induced,  enzymology*
Calcinosis / chemically induced,  enzymology*
Calcium / analysis
Calcium Chloride / toxicity*
Capillary Permeability / drug effects
Desmosine / analysis
Elastic Tissue / drug effects,  pathology*
Elastin / metabolism*
Endothelium, Vascular / drug effects,  metabolism
Extracellular Matrix / pathology
Male
Matrix Metalloproteinase 2 / deficiency,  genetics,  physiology*
Matrix Metalloproteinase 9 / deficiency,  genetics,  physiology*
Mice
Mice, Knockout
Rats
Rats, Sprague-Dawley
Tunica Media / drug effects,  pathology*
Grant Support
ID/Acronym/Agency:
HL61652/HL/NHLBI NIH HHS; R01 HL061652/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
11003-57-9/Desmosine; 9007-58-3/Elastin; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9; M4I0D6VV5M/Calcium Chloride; SY7Q814VUP/Calcium
Comments/Corrections

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


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