Matrix metalloproteinases. Their role in degenerative chronic diseases of abdominal aorta

Background. The main chronic degenerative diseases of the abdominal aorta, namely aneurysmatic and steno-obstructive pathologies, have a common denomi nator: atherosclerosis. Both pathologies are characterised by the destructi on of the structural integrity of the extracellular protein matrix (ME). A number of studies have shown the presence and involvement of a group of enz ymes with proteolytic activity towards one or more ME components, the matri x metalloproteinases (MMPs), in the pathogenesis of aneurysms of the abdomi nal aorta. Other authors have underlined the role of MMPs in the proliferat ion and migration process of smooth muscle cells into the intima in the pat hogenesis of atheromasic plaque. The aim of this study was to evaluate the possible role of these enzymes in the pathogenesis of chronic degenerative diseases of the aorta. Methods. Fragments of aortic wall were removed from patients undergoing ele ctive aortic surgery for aneurysms (14 patients) or aortic steno-obstructio n (4 patients). The samples obtained were treated appropriately and then su bject to immunohistochemical analysis. The preparations were incubated with specific anti-MMP antibodies and were also incubated with substrate and ch romogen, forming a pigmented precipitate on the site of the antigen, before being observed using an optic microscopic at an enlargement of 250x. Nucle ar positivity linked to the presence of the antigen testified the validity of staining. Lastly, the MMP INDEX, or in other words the number of positiv e cells out of 100, was stained in the adventitia and in the tunica media i n each preparation. Results. MMPs were divided into three main groups: interstitial collagenase (MMP1) which degrade type I and III native collagen; gelatinases (MMP9, MM P2) which act on elastin and type IV collagen; stromelysins (MMP3) with spe cific proteolytic action towards proteoglycans, fibronectin and laminine. I n our experience, those preparations obtained from aorta affected by steno- obstructive pathologies (4 patients) revealed the presence of MMPs with a p referential localisation on the intimal side of the tunica media. In partic ular, the increased activity of gelatinases MMP3 in atherosclerotic aorta m ight be responsible for destroying the internal elastic lamina and fosterin g the proliferation and migration of smooth muscle cells and the formation of atheromasic plaque. On the other hand, preparations obtained from aneury smatic aorta (14 patients) showed an opposite situation with a preferential localisation within the adventitia and on the adventitial side of the medi a Above all, the loss of elastin represents an essential stage in the forma tion of aortic aneurysms. Conclusions. This study concords with numerous authors who have demonstrate d the involvement of proteinase MMPs in the development of aortic aneurysms and their possible role in the pathogenesis of atheromasic plaque. The dif ferent origin of these enzymes (inflammatory cells and macrophages or endot helial cells) may be the result of different pathogenetic mechanisms. Altho ugh they present different pathogenetic features, aortic aneurysms and sten o-obstructions have a common denominator in atherosclerosis. The mechanisms responsible for their evolution towards one or other form are not known. T he different expression of MMPs in the context of the aortic wall represent s a field for future research.