Characterization of an elastase from aneurysmal aorta which degrades intact aortic elastin.
Accumulating evidence suggests that abdominal aortic aneurysms (AAA) are due to a pathologic process which results in the destruction of aortic elastin and other matrix components. In this study, protein extractions were performed on both aneurysmal and normal aorta. Extracts were applied to frozen section of normal aorta either alone or in combination with 10 mM ethylenediaminetetraacetic acid, recombinant tissue inhibitor of metalloproteases, 10 mM zinc, and 5 mM phenylmethylsulfonyl fluoride, under conditions where calcium was removed from the buffer. After incubation, the sections were stained for elastin and evaluated by computerized morphometry. Aneurysm extracts, only in the presence of calcium, showed significant elastolytic activity characterized by destruction of intact elastic lamellae that was inhibited by ethylenediaminetetraacetic acid, the recombinant metalloprotease inhibitor, and zinc. Phenylmethylsulfonyl fluoride showed no inhibitory activity. Healthy aortic extract showed no elastolytic activity. This inhibitory profile is consistent with a metalloenzyme. We conclude that aneurysmal aorta contains elastolytic activity that is secondary to a metalloenzyme which is not present in normal aorta. This activity may play a role in the destruction of the elastin matrix that is seen in AAA's.
Reilly
J M
JM
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Brophy
C M
CM
Tilson
M D
MD
D001012:Aorta, Abdominal / Q000201:enzymology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology*; D004492:Edetic Acid / Q000494:pharmacology; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D008666:Metalloendopeptidases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D010196:Pancreatic Elastase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000302:isolation & purification*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D014020:Tissue Extracts / Q000032:analysis / Q000302:isolation & purification; D015032:Zinc / Q000494:pharmacology
D014020:Tissue Extracts; D010664:Phenylmethylsulfonyl Fluoride; D004549:Elastin; D004492:Edetic Acid; D010196:Pancreatic Elastase; D008666:Metalloendopeptidases; D015032:Zinc