Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm.
A prominent metalloproteinase activity with an apparent molecular mass of 80 kD and additional activities at 67 through 70, 50, and 32 kD have been observed on casein, gelatin, and elastin gel zymography in extracts from abdominal aortic aneurysms (AAAs). The forms at 80, 50, and 32 kD were isolated by affinity to recombinant tissue inhibitor of metalloproteinases, and the 80-kD and 50-kD components were shown to be derived from matrix metalloproteinase-9 (MMP-9). The relative electrophoretic mobility of these forms under reducing and nonreducing conditions corresponds to those of MMP-9 generated by MMP-3 (stromelysin-1) cleavage, and the active forms of MMP-3 at 45 and 35 kD were detected in aneurysmal extracts under reducing conditions by using specific antibody. Confirmation that the major proteolytic activity observed at 80 kD is MMP-9 was also demonstrated by immunoprecipitation of the activity with specific antibody. Comparative immunoblots of tissue extracts from 10 typical AAA patients, using specific antibody against MMP-9, revealed bands at 92, 82, 67, 51 through 53, 27, 23, and 20 kD under reducing conditions; six aortic control specimens displayed negligible immunoreactivity. This report is the first to show that known activated forms of MMP-3 and MMP-9 are present in the aneurysmal aortic wall and that they may play a role in the destruction of aortic matrix in AAA disease.
Newman
K M
KM
Columbia University, New York, NY.
Ogata
Y
Y
Malon
A M
AM
Irizarry
E
E
Gandhi
R H
RH
Nagase
H
H
Tilson
M D
MD
D001012:Aorta, Abdominal; D001014:Aortic Aneurysm / Q000201:enzymology*; D017364:Collagenases / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000737:chemistry; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000032:analysis* / Q000737:chemistry; D011233:Precipitin Tests
D007527:Isoenzymes; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9