PRODUCTION AND LOCALIZATION OF 92-KILODALTON GELATINASE IN ABDOMINAL AORTIC-ANEURYSMS - AN ELASTOLYTIC METALLOPROTEINASE EXPRESSED BY ANEURYSM-INFILTRATING MACROPHAGES

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.