Matrix metalloproteinases in abdominal aortic aneurysm: characterization, purification, and their possible sources.
One of the most consistent observations in abdominal aortic aneurysm (AAA) disease is the disorganization and disruption of elastin and other matrix components of the aortic wall. The enzymatic basis for the biochemical features of AAA has been investigated beginning with the demonstration on substrate gel enzymography of a typical "profile" of proteinase activities in AAA tissue extracts which degrade gelatin, casein and elastin. A recombinant TIMP-1 affinity column was developed and three of the elastolytic/caseinolytic activities with approximate molecular weights of approximately 80 kDa, approximately 50 kDa and approximately 32 kDa were partially purified from these extracts. Affinity for rTIMP-1 suggests that these enzymes are members of the matrix metalloproteinase (MMP) family. High molecular weight forms of two MMPs, collagenase (MMP-1) and stromelysin-1 (MMP-3), were also isolated from the AAA tissue on this column; active forms of MMP-1 could be demonstrated by immunoblotting techniques in this preparation under reducing conditions. Infiltrating inflammatory cells are known sources of these proteolytic activities; analysis of these cell populations in the aneurysmal aortic wall using fluorescence-activated cell counting revealed a fifty-fold increase in macrophages (a well-known source of matrix-degrading enzymes) as well as a significant increase in lymphocytes.
Columbia University, St. Lukes/Roosevelt Hospital Center, Department of Surgery, New York, NY 10019.
K M
KM
Newman
A M
AM
Malon
R D
RD
Shin
J V
JV
Scholes
W G
WG
Ramey
M D
MD
Tilson
D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology*; D001161:Arteriosclerosis / Q000378:metabolism; D002469:Cell Separation; D017364:Collagenases / Q000378:metabolism; D005109:Extracellular Matrix / Q000201:enzymology*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000302:isolation & purification* / Q000378:metabolism*
D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3