The Role Matrix Metalloproteinases in the Production of Aortic Aneurysm

Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle cells in the aortic media and the destruction of extracellular matrix (ECM). Furthermore, AAA have evidence of inflammation and the cellular elements involved in inflammation such as macrophages can produce and/or activate MMPs This chapter focuses on human aortic aneurysm that are not due to specific known genetic causes because this type of aneurysm is the more common type. This chapter will also focus on MMP protein expression rather than on genetic data which may not necessarily translate to increased MMP protein expression. There are supporting data that certain MMPs are increased in the aortic wall. For TAA, it is most notably MMP-1, -9, -12, and -14 and MMP-2 when a bicuspid aortic valve is present. For AAA, it is MMP-1, -2, -3, -9, -12, and -13. The data are weaker or insufficient for the other MMPs. Several studies of gene polymorphisms support MMP-9 for TAA and MMP-3 for AAA as potentially important factors. The signaling pathways in the aorta that can lead to MMP activation include JNK, JAK/stat, osteopontin, and AMP-activated protein kinase alpha2. Substrates in the human vasculature for MMP-3, MMP-9, or MMP-14 include collagen, elastin, ECM glycoprotein, and proteoglycans. Confirmed and potential substrates for MMPs, maintain aortic size and function so that a reduction in their content relative to other components of the aortic wall may produce a failure to maintain aortic size leading to dilatation and aneurysm formation.