Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases.
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.


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.
Basalyga
Dina M
DM
Department of Bioengineering, Clemson University, Clemson, SC 29634, USA.
Simionescu
Dan T
DT
Xiong
Wanfen
W
Baxter
B Timothy
BT
Starcher
Barry C
BC
Vyavahare
Narendra R
NR
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000139:chemically induced / Q000201:enzymology*; D002114:Calcinosis / Q000139:chemically induced / Q000201:enzymology*; D002118:Calcium / Q000032:analysis; D002122:Calcium Chloride / Q000633:toxicity*; D002199:Capillary Permeability / Q000187:drug effects; D003895:Desmosine / Q000032:analysis; D004547:Elastic Tissue / Q000187:drug effects / Q000473:pathology*; D004549:Elastin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology*
D003895:Desmosine; D004549:Elastin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002122:Calcium Chloride; D002118:Calcium