The events that result in the establishment and progression of
aortic aneurysms are complex and multifactorial. However, degradation of the extracellular matrix (ECM) of aortic tunica media appears to be a consistent histopathological and biochemical feature. An increased local expression of
matrix metalloproteinases (
MMPs) as well as an imbalance between
MMP expression and the expression of their natural tissue inhibitors (TIMPs) have been demonstrated in dilated aortic wall. We hypothesized that a distinct
MMP and TIMP expression pattern underlies the development of ascending aorta dilation. To test our hypothesis, expression levels of 10
MMPs and 4 TIMPs were assessed by real-time PCR in dilated and normal aortic tissue derived from patients that underwent elective surgical repair of
ascending aorta aneurysm (AAA) and coronary artery by-pass grafting, respectively. We found no statistically significant up- or down-regulation of any individual
MMP. Surprisingly, the
tissue inhibitor of metalloproteinases (TIMP)-3 was significantly more expressed in dilated aortic tissue compared to control tissue, thereby reflecting an effort to counteract
MMP activity. Finally, when we evaluated the
MMP and TIMP co-expression pattern in normal and dilated aortic tissue, we observed that in
aortic aneurysms activation of the
MMP system was characterised by the co-expression of more than one
proteinase and the down-regulation of
TIMP-1 and -2. The latter observation is the key regulatory point that leads to ECM degradation and, subsequently, to AAA formation.