Role of matrix metalloproteinases in abdominal aortic aneurysms

Considerable progress has been made toward characterizing the enzymes and proteolytic events that occur in established human abdominal aortic aneurysms (AAA). Through studies involving a number of different laboratories and various experimental approaches, enzymes of the matrix metalloproteinase (MMP) family have consistently emerged as important molecular participants in aneurysm disease. The finding that elastolytic MMPs, particularly MMP-9 and MMP-2, are expressed and produced in increased amounts in human aneurysm tissue, has led to the possibility that these enzymes might serve as rational targets for pharmacotherapy in this disease. Recent studies using MMP-inhibiting tetracycline derivatives in the elastase-induced rodent model of AAA indicate that metalloproteinase suppression is a feasible and successful approach in the experimental setting. The definitive proof-of-principle for the therapeutic efficacy of anti-MMP or other anti-proteinase strategies to limit the growth of small AAA, however, will remain unknown until specifically tested in clinical trials.