Matrix metalloproteinases: contribution to pathogenesis, diagnosis, surveillance and treatment of abdominal aortic aneurysms

Background: Aortic abdominal aneurysm (AAA) represents a common chronic degenerative disease of the aortic wall. Chronic inflammation and enzymatic degradation of elastic lamellae and extracellular matrix (ECM) proteins constitute the most prominent characteristics of AAAs. There is mounting evidence that matrix metalloproteinases (MMPs) are the predominant proteinases in the AAA wall. These enzymes represent a potential target for therapeutic intervention to modify vascular pathology. This paper is an overview of matrix metalloproteinases and their role in the pathophysiology, diagnosis and treatment of AAA. Literature search: Comprehensive search of the MEDLINE, EMBASE and HEAL-Link databases from 1980 to 2003. Findings: Increased levels of MMPs expression and activity have been demonstrated within the aortic wall of AAA, associating with histological alterations. An imbalance between MMPs and their inhibitors (Tissue Inhibitors of Matrix Metalloproteinases - TIMPs), may tip the equilibrium towards matrix degradation. MMPs as systemic biochemical markers of AAAs may contribute to diagnosis of unsuspected AAAs or to the surveillance of patients with small AAAs. Evidence of variations in MMPs, TIMPs and their mediator genes promoting the increased inheritance susceptibility of AAAs is less well documented. However, a broad spectrum of pharmaceutical agents (e.g. doxycycline, statins etc.) is known to inhibit MMP activity and attenuate medial destruction. Conclusion: Randomized clinical studies in patients in the early stages of AAA or in healthy individuals with great propensity to AAA development are required to demonstrate the causative relationship between MMPs and AAA. It still remains obscure whether long-term administration of MMP inhibitors can decelerate or even prevent the need for surgical repair.