Proteinase Systems and Thoracic Aortic Aneurysm Progression

Thoracic aortic aneurysms (TAAs) are a rare but potentially devastating condition. Current surgical treatment of TAAs usually involves a major operation, which conveys many risks to the patient. Better knowledge of the cellular events that lead to aneurysm formation may elucidate less morbid treatment options for this condition. A number of recent studies have identified that the relative abundance and activity of extracellular matrix (ECM) proteolytic systems are increased with TAAs. Specifically, the matrix metalloproteinases (MMPs) have been linked through numerous studies to TAA formation.MMPs comprise a family of ECM-degrading proteinases. Endogenous tissue inhibitors (TIMPs) normally regulate MMP activity, and the activation of MMPs is complex and tightly controlled. Aneurysm formation may be related to relative changes in the balance between MMP/TIMP abundance favoring proteolysis. Through ECM degradation, the medial layer will undergo structural remodeling and a loss of structural integrity, leading to TAA formation.The goals of this review are to examine the structure of the normal and aneurysmal thoracic aorta and to place the new findings regarding ECM proteolysis in perspective with regard to TAA formation and progression. Through an integration of basic and clinical studies regarding the underlying molecular basis for proteolysis of the thoracic aorta, improved diagnostic, prognostic, and therapeutic strategies for this disease process are likely to be realized.