**6. Possible diagnostic markers**

68 Aneurysm

13].

aneurysm [14, 15].

development of AAA [16].

MMP-12 [8].

Nishimura *et al.* also observed a significant correlation of the expression of MMP-2 and

The degeneration of collagen and elastin leading to the development of aneurysms is a multifactorial process. Various factors may take part in the stimulation of both cells constituting the arterial wall and cells infiltrating it to produce MMPs. Aortic wall is subjected to cyclic stretching because of pulsative blood flow which is a normal physiological condition. AAA is often accompanied by an intraluminal thrombus. It causes that some cells within the aneurysm may be subjected to hypoxia. Experimental study of Oya *et al*. revealed that macrophages cultured in conditions subjected to cyclic stretching under normoxia and hypoxia which simulated the pulsative blood flow and hypoxia due to thrombus presented an increased MMP-9 production. These macrophages produced interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) leading to increased apoptosis of vascular smooth muscle cells. Hypoxia was also demonstrated to augment the expression of MMP-1, MT-1 MMP, MMP-2, MMP-7 and MMP-9 in SMC derived from human aorta [12,

Nowadays many scientists focus their research on finding new factors which may augment the secretion of metalloproteinases by the cells present in aneurysms. Experimental studies confirmed that stenosis resulting in a turbulent blood flow can be the next factor increasing expression of MMP-2 and MMP-9 within abdominal aortic aneurysm. Interesting results were obtained by Stolle *et al*. Mice exposed to cigarette smoke and angiotensin II treatment had increased the incidence of AAA and higher gene expression of MMP-2, MMP-3, MMP-8, MMP-9 and MMP-12 in aorta and increased proteolytic activity of two most investigated metalloproteinaes, MMP-2 and MMP-9. Although each of this two factors alone induced minor changes, their combination accelerated the pathologic process. Exposure of the arterial wall to an increased concentration of angiotensin II represents conditions that may be observed in patients with arterial hypertension. This experiment demonstrates that coexistance of arterial hypertension and smoking augments the risk of a development of

Studies of Zhang *et al*. demonstrated that human AAA tissues had elevated levels of advanced glycation end products (AGEs) and their receptor (RAGE). In experimental model this group of researchers observed that AGEs induce the production of MMP-9 by macrophages. An increased serum concentration of AGEs accompanies poorly controlled diabetes mellitus. These results indicate that such patients may be at a greater risk of a

Abdominal aortic aneurysm is characterized not only by the destruction of its structural integrity of the extracellular matrix protein and inflammatory infiltrate but also by intensive neovascularisation. These new blood vessels developing inside the arterial wall in a place of growing aneurysm are the next source of metalloproteinases degrading ECM. Immature neovessels express MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9 and

MMP-9 and between each of these metalloproteinases and TIMP-1 [6].

The results of scientific researches discussed so far concern the evaluation of either expression or activity of MMPs in the tissue obtained from aneurysms in humans or experimental animals. These measurements have the scientific importance but cannot serve as a diagnostic marker. A growing interest is focused on finding circulating predictors of risk of the development of aneurysm or plasma markers of existing, yet undiagnosed aneurysm. Plasma levels of MMPs are of great interest. MMP-2 and MMP-9 are the candidates for such markers. Polish researchers observed significantly higher plasma concentration of MMP-9 in patients with AAA and thin intraluminal thrombus than in patients with abdominal aortic aneurysm and thick thrombus. Hellenthal *et al.* points out that plasma level of MMP-9 may serve as a marker discriminating patients with and without endoleak within AAA [18-20].

Several polymorphisms of metalloproteinases have been discovered. Their role in the development of AAA is being studied. The polymorphisms of MMP-2 (1306C/T), MMP-3 (5A/6A) and MMP-13 (77A/G) may contribute to the pathogenesis of AAA. The studies of circulating markers of aneurysms give promising results but further research is still required [21].
