Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms.
Degradation of the elastic media is a hallmark of abdominal aortic aneurysms (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from atherosclerotic occlusive disease (AOD) and nondiseased control tissues. Quantitative competitive reverse transcription-polymerase chain reaction and gelatin zymography showed increased MMP-9 mRNA and protein in both AAA and AOD tissues compared with those in control tissue, but there was no significant difference between AAA and AOD. In contrast, MMP-2 mRNA and protein levels were significantly higher in AAA than in AOD or control tissues. Sequential extraction of the MMPs from the aortic tissue with a physiological salt solution, 2% dimethylsulfoxide (DMSO), and 10 mol/L urea showed that large amounts of MMP-2 and MMP-9 were bound to the matrix. The most conspicuous finding was that the levels of MMP-2 were significantly elevated in the DMSO fraction in AAA tissues compared with AOD and control tissues. In addition, a large portion of MMP-2 found in the DMSO and urea fractions was in the active 62-kDa form, indicating that the precursor of MMP-2 in AAA is largely activated locally and binds to the tissue matrix tightly. By immunolocalization, MMP-9 was found to be primarily produced by macrophages and MMP-2 by mesenchymal cells. The production of MMP-2 was prominent when mesenchymal cells were surrounded by inflammatory cells, suggesting paracrine modulation of MMP-2 expression in AAAs. These observations emphasize that MMP-2 participates in the progression of AAAs by degrading aortic tissue matrix components.
Departments of Surgery and of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, USA.
V
V
Davis
R
R
Persidskaia
L
L
Baca-Regen
Y
Y
Itoh
H
H
Nagase
Y
Y
Persidsky
A
A
Ghorpade
B T
BT
Baxter
D000368:Aged; D001012:Aorta, Abdominal / Q000201:enzymology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology*; D017364:Collagenases / Q000032:analysis / Q000235:genetics; D018093:Gelatinases / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger
D012333:RNA, Messenger; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9