Matrix metalloproteinases in aortic aneurysm - executors or executioners?

Abstract

Despite numerous studies focusing on the aortic aneurysm pathogenesis, the mechanism of aneurysm formation, especially – initiation of this process, remains unclear. The research concerning both, structural and molecular studies, is based on two main data sources. The first source of information are patients with already formed aneurysm, and with well defined biochemical and morphological changes in aortic wall architecture. The other source of data are experimental studies based on laboratory animals with artificially induced aneurysms. This approach enables verification of various hypotheses concerning pathogenesis of aortic aneurysm. Regrettably, animal aneurysm models, although similar, are not exactly the same, as human pathology. Thus, since the link between both mentioned data sources is still lacking, the knowledge achieved to date, even being highly profound, is not sufficient to fully understand this disease. Besides well defined factors, predisposing to formation of aortic aneurysm (patient’s age, cigarette smoking, arterial hypertension, atherosclerosis, as well as the Marfan’s and the Ehlers-Danlos’s syndrome-associated mutations), increasing popularity is currently being gained by the hypothesis concerning the pivotal role of proteolytic enzymes matrix metalloproteinases (MMPs) in aortic wall destruction. The involvement of MMPs in extracellular matrix damage in aortic aneurysm is doubtless. However, it needs to be elucidated, what the sequence of events is and what the exact role of MMPs is in these events. MMPs could play a role of “executioners”, that are produced and activated in the aortic wall as constituents of inflammatory reaction, in response to some yet poorly defined triggers. On the other hand, it is plausible, that aortic wall destruction, followed by inflammatory response to tissue degradation products, results from primary local overproduction and/or activation of proteases. It could be due to some mutations or polymorphisms of MMP genes, or some impairment in their controlling mechanisms. In that circumstance MMPs could rather be considered as “executors”, with causative role in aortic aneurysm pathogenesis. Although the majority of studies suggest the first scenario as being more possible, there is some evidence, that could support the second alternative, too.