Connective tissue proteinases and inhibitors in abdominal aortic aneurysms. Involvement of the vasa vasorum in the pathogenesis of aortic aneurysms.
Recent studies have shown that increases in proteolytic activity are associated with abdominal aortic aneurysms (AAAs). We have studied samples of the dilated aortic wall, taken during corrective surgery for AAAs, in terms of the number, type, and tissue location of connective tissue proteinases and their inhibitors. Five distinct caseinolytic serine proteinases and six gelatinolytic metalloproteinases were resolved by molecular weight by use of sodium dodecyl sulfate-substrate gel electrophoresis. Isoforms of the Mr 92,000 neutrophil gelatinase were identified by immunoprecipitation of biosynthetically labeled organ culture media. About 50% of the total radiolabeled protein secreted by AAA organ cultures was identified as the Mr 30,000 glycoprotein, tissue inhibitor of metalloproteinase (TIMP), by immunoprecipitation. Both TIMP and gelatinase were localized to the vasa vasorum by immunoperoxidase staining. However, interstitial collagenase could not be detected by any method. These results suggest the involvement of the vasa vasorum in the maintenance and possibly the genesis of AAAs.
Laboratory of Radiobiology, University of California at San Francisco.
G S
GS
Herron
E
E
Unemori
M
M
Wong
J H
JH
Rapp
M H
MH
Hibbs
R J
RJ
Stoney
D001012:Aorta, Abdominal / Q000378:metabolism*; D001014:Aortic Aneurysm / Q000209:etiology / Q000378:metabolism*; D003238:Connective Tissue / Q000201:enzymology*; D003902:Detergents; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D004792:Enzyme Precursors / Q000737:chemistry; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008666:Metalloendopeptidases / Q000032:analysis; D009924:Organ Culture Techniques; D011506:Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases; D014651:Vasa Vasorum / Q000502:physiology*
D003902:Detergents; D004792:Enzyme Precursors; D006023:Glycoproteins; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D010450:Endopeptidases; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases