MMP-12 has a role in abdominal aortic aneurysms in mice.
BACKGROUND
Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess the role of MMP-12 in aneurysm formation.


METHODS
A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium chloride (CaCl 2 ) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-12 -/- ) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta.


RESULTS
There is an increase of 63 +/- 5% (mean +/- SEM) in aortic diameters of WT mice after CaCl 2 inductions, while MMP-12 -/- mice increased only 26 +/- 14%. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12 -/- mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl 2 treatment, whereas no MMP-12 was detected in MMP-12 -/- mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12 -/- mice. Immunohistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12 -/- mice were significantly less than WT controls.


CONCLUSIONS
MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment.
Longo
G Matthew
GM
Department of Surgery, University of Nebraska Medical Center, 8111 Dodge Street, Omaha, NE 68114, USA. btbaxter@unmc.edu
Buda
Steven J
SJ
Fiotta
Nicola
N
Xiong
Wanfen
W
Griener
Timothy
T
Shapiro
Steven
S
Baxter
B Timothy
BT
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D002122:Calcium Chloride; D004195:Disease Models, Animal; D007700:Kinetics; D008264:Macrophages / Q000473:pathology; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12; D002122:Calcium Chloride