PRODUCTION AND LOCALIZATION OF 92-KILODALTON GELATINASE IN ABDOMINAL AORTIC-ANEURYSMS - AN ELASTOLYTIC METALLOPROTEINASE EXPRESSED BY ANEURYSM-INFILTRATING MACROPHAGES
Rw. Thompson et al., PRODUCTION AND LOCALIZATION OF 92-KILODALTON GELATINASE IN ABDOMINAL AORTIC-ANEURYSMS - AN ELASTOLYTIC METALLOPROTEINASE EXPRESSED BY ANEURYSM-INFILTRATING MACROPHAGES, The Journal of clinical investigation, 96(1), 1995, pp. 318-326
Abdominal aortic aneurysms (AAA) are characterized by disruption and d
egradation of the elastic media, yet the elastolytic proteinases invol
ved and their cellular sources are undefined. We examined if 92-kD gel
atinase, an elastolytic matrix metalloproteinase, participates in the
pathobiology of AAA. Gelatin zymography of conditioned medium from nor
mal, atheroocclusive disease (AOD), or AAA tissues in organ culture sh
owed that all tissues produced 72-kD gelatinase. AOD and AAA cultures
also secreted 92-kD gelatinase, but significantly more enzyme was rele
ased from AAA tissues. ELISA confirmed that AAA tissues released simil
ar to 2-fold more 92-kD gelatinase than AOD tissue and similar to 10-f
old more than normal aorta. Phorbol ester induced a 5.3-fold increase
in 92-kD gelatinase secretion by normal aorta and AOD and an 11.5-fold
increase by AAA. By immunohistochemistry, 92-kD gelatinase was not de
tected in normal aorta and was only occasionally seen within the neoin
timal lesions of AOD tissue. In all AAA specimens, however, 92-kD gela
tinase was readily localized to numerous macrophages in the media and
at the adventitial-medial junction. The expression of 92-kD gelatinase
mRNA by aneurysm-infiltrating macrophages was confirmed by in situ hy
bridization, These results demonstrate that diseased aortic tissues se
crete greater amounts of gelatinolytic activity than normal aorta prim
arily due to increased production of 92-kD gelatinase. In addition, th
e localization of 92-kD gelatinase to macrophages in the damaged wall
of aneurysmal aortas suggests that chronic release of this elastolytic
metalloproteinase contributes to extracellular matrix degradation in
AAA.