A disturbance of the structure of the aortic wall results in the formation of aortic aneurysm, which is characterized by a significant bulge on the vessel surface that may have consequences, such as distention and finally rupture. Abdominal aortic aneurysm (AAA) is a major pathological condition because it affects approximately 8% of elderly men and 1.5% of elderly women. The pathogenesis of AAA involves multiple interlocking mechanisms, including inflammation, immune cell activation, protein degradation and cellular malalignments. The expression of inflammatory factors, such as cytokines and chemokines, induce the infiltration of inflammatory cells into the wall of the aorta, including macrophages, natural killer cells (NK cells) and T and B lymphocytes. Protein degradation occurs with a high expression not only of matrix metalloproteinases (MMPs) but also of neutrophil gelatinase-associated lipocalin (NGAL), interferon gamma (IFN-γ) and chymases. The loss of extracellular matrix (ECM) due to cell apoptosis and phenotype switching reduces tissue density and may contribute to AAA. It is important to consider the key mechanisms of initiating and promoting AAA to achieve better preventative and therapeutic outcomes.

• MeSH
• aneurysma břišní aorty * metabolismus   MeSH
• aorta metabolismus   MeSH
• apoptóza genetika   MeSH
• cytokiny metabolismus   MeSH
• fenotyp MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Information about the tissue characteristics of abdominal aortic aneurysms (AAAs), some of which may be reflected in the serum, can help to elucidate AAA pathogenesis and identify new AAA biomarkers. This information would be beneficial not only for diagnostics and follow-up but also for potential therapeutic intervention. Therefore, the aim of our study was to compare the expression of structural proteins, immune factors (T and B lymphocytes, macrophages, neutrophils and pentraxin 3 (PTX3)), osteoprotegerin (OPG), microvessels and hypoxic cells in AAA and nonaneurysmal aortic walls. We examined specimens collected during surgery for AAA repair (n = 39) and from the abdominal aortas of kidney donors without AAA (n = 8). Using histochemical and immunohistochemical methods, we quantified the areas positive for smooth muscle actin, desmin, elastin, collagen, OPG, CD3, CD20, MAC387, myeloperoxidase, PTX3, and hypoxia-inducible factor 1-alpha and the density of CD31-positive microvessels. AAA samples contained significantly less actin, desmin, elastin and OPG, more collagen, macrophages, neutrophils, T lymphocytes, B lymphocytes, hypoxic cells and PTX3, and a greater density of vasa vasorum (VV) than those in non-AAA samples. Hypoxia positively correlated with actin and negatively correlated with collagen. Microvascular density was related to inflammatory cell infiltrates, hypoxia, PTX3 expression and AAA diameter. The lower OPG expression in AAAs supports the notion of its protective role in AAA remodeling. AAA contained altered amounts of structural proteins, implying reduced vascular elasticity. PTX3 was upregulated in AAA and colocalized with inflammatory infiltrates. This evidence supports further evaluation of PTX3 as a candidate marker of AAA. The presence of aortic hypoxia, despite hypervascularization, suggests that hypoxia-induced neoangiogenesis may play a role in AAA pathogenesis. VV angiogenesis of the AAA wall increases its vulnerability.

• MeSH
• aneurysma břišní aorty etiologie   metabolismus   patologie   MeSH
• biologické markery MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• hypoxie metabolismus   MeSH
• imunohistochemie MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoprotegerin metabolismus   MeSH
• patologická angiogeneze metabolismus   MeSH
• senioři MeSH
• sérový amyloidový protein metabolismus   MeSH
• studie případů a kontrol MeSH
• zánět komplikace   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Abdominal aortic aneurysm (AAA) is a serious condition of unclear pathogenesis and progression. Two samples were collected from 48 patients during AAA surgery. One sample was collected from the aneurysm, the other from the aneurysm proximal neck where the tissue did not exhibit any aneurysmal changes. Subsequently, gene expression profiles using microarrays (Illumina) were compared in RNA extracted from the samples. Overall, 2,185 genes were found to be upregulated and 2,100 downregulated; from which 158 genes had a different expression with FDR<0.05 (False Discovery Rate) and FC>/=2 (Fold Change). Of this number, 115 genes were over-expressed and 43 under-expressed. The analysis of the gene list based on their biological pathways revealed that the regulation of inflammation was mediated by chemokine and cytokine signaling pathways, the integrin signaling pathway, and T and B cell activation. Moreover, a change was identified in the expression of genes involved in both intercellular and intracellular signaling systems.

• MeSH
• aneurysma břišní aorty genetika   imunologie   metabolismus   MeSH
• exprese genu fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu imunologie   metabolismus   MeSH
• senioři MeSH
• stanovení celkové genové exprese metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a complex role in the pathogenesis of atherosclerosis. We compared (1) the histopathological findings in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD); (2) the expression of MMP-2/MMP-9 and TIMP-1/TIMP-2 in aortic layers, inflammatory cells and smooth muscle cells (SMCs), aiming to identify the common underlying pathogenic mechanisms of the disease development. Samples were obtained from 30 patients with AAA and 30 with AOD. Aortic histology and immunohistochemistry were performed to evaluate inflammatory changes and MMP and TIMP expression. Thrombosis and ulceration were more frequent in AOD than in AAA. The MMP-9 expression was elevated in all aortic layers of AAA patients and in media/adventitia of AOD patients, mainly followed by lower expression of its inhibitor TIMP-1. Higher MMP-9 expression was also found in SMCs and macrophages of both AAA and AOD specimens, while higher TIMP-1/TIMP-2 were predominantly observed in the lymphocytes and macrophages of the aneurysm. These results showed that both conditions exhibited increased MMP-9 expression; however, the MMP expression pattern differed to some degree between the aneurysms and occlusive disease. The variations in molecular mechanisms underlying dilatative/stenosing disease warrant further investigation.

• MeSH
• aneurysma břišní aorty metabolismus   MeSH
• arteriální okluzní nemoci metabolismus   MeSH
• imunohistochemie MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• myocyty hladké svaloviny metabolismus   MeSH
• nemoci aorty metabolismus   MeSH
• tkáňový inhibitor metaloproteinasy 1 metabolismus   MeSH
• tkáňový inhibitor metaloproteinasy 2 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSES: A ruptured AAA (rAAA) is a common cause of death in males over 60 years of age, and the global mortality from rAAA exceeds 80 %. The pathological processes occurring in the wall of the developing AAA are still unclear. The potential pathophysiological mechanisms underlying aortic aneurysms have been examined by many studies using immunohistochemistry and were, therefore, targeted at specific, preselected protein antigens. METHODS: We collected samples of tissue from anterior wall of an aneurysm sac from 15 patients indicated for AAA resection (group A) during the period from 2010 to 2011. These samples were subjected to a proteomic analysis. In addition, we collected control samples of identical aortic tissue from 10 heart-beating deceased organ donors (group B). RESULTS: A total of 417 differentially expressed protein fractions were identified, 18 of which were only detected in the healthy controls, while 85 were specific for aneurysm tissue and 314 were detectable in both groups. In 175 protein fractions, the gel-derived spot volumes differed significantly between aneurismal and healthy aortic tissue. CONCLUSIONS: We found a significant difference in the proteome of the AAA tissue and non-dilated aortic tissue. We demonstrated that the AAA proteome is considerably richer and more varied than the healthy and atherosclerotic aorta. We believe that our results clearly demonstrate a completely different etiopathogenesis of atherosclerosis and aneurismal disease.

• MeSH
• 2D gelová elektroforéza MeSH
• aneurysma břišní aorty genetika   metabolismus   MeSH
• ateroskleróza genetika   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• proteom genetika   metabolismus   MeSH
• proteomika * metody   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a serious disease due to its covert nature, relatively high prevalence and fatal prognosis in the case of rupture. To obtain new insights into AAA pathogenesis, we examined the relationships between histopathology, multiplex in vitro immunoassay data, diameter and symptomatology. METHODS: In a prospective, non-randomised study, we evaluated samples from 6 normal infrarenal aortae and 65 AAA patients (65 walls, 55 thrombi). The AAA patients were either asymptomatic (n = 44), symptomatic (n = 7) or with ruptured AAA (n = 14). The AAA diameter was classified as small (<5 cm, n = 18), medium (5-7 cm, n = 26) and large (>7 cm, n = 21). We quantified the histopathology of the AAA wall and the adjacent thrombus. We assessed the expression of proteins in the same samples. RESULTS: Asymptomatic AAAs had walls with more abundant inflammatory infiltrates, lower amounts of PAI-1, a higher number of tPA-positive elements, a tendency towards decreased collagen content, whereas the adjacent thrombi had a greater concentration of VCAM-1 and MMP-2 when compared with symptomatic AAAs. Compared with the aneurysmatic aorta, the normal aorta contained less collagen and more elastin, actin, desmin and PAI-1-positive elements; in addition, it was more vascular. Medium-sized AAAs were the most actin and vimentin rich, and large AAAs were the most vascular. CONCLUSION: Our results show that asymptomatic AAA walls often have more potentially deleterious histopathological alterations than symptomatic AAA walls. This result indicates that a progression from an asymptomatic AAA to rupture can be expected and screening patients who are at risk of rupture could be beneficial.

• MeSH
• aktiny metabolismus   MeSH
• aneurysma břišní aorty metabolismus   patologie   MeSH
• aorta abdominalis metabolismus   patologie   MeSH
• asymptomatické nemoci MeSH
• cévní buněčněadhezivní molekula-1 metabolismus   MeSH
• desmin metabolismus   MeSH
• dospělí MeSH
• elastin metabolismus   MeSH
• extracelulární matrix metabolismus   MeSH
• histocytochemie MeSH
• inhibitor aktivátoru plazminogenu 1 metabolismus   MeSH
• kolagen metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• ruptura aorty metabolismus   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• trombóza metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cytosol levels of cytokines [interleukins 1b, 6, 8 (IL-1b, 6, 8), tumor necrosis factor-alpha (TNF-alpha)] in aneurysm walls were evaluated in a prospective non-randomized study of 57 patients. The group was divided into two subgroups: Subgroup I (ruptured aneurysms, n=11) and Subgroup II (asymptomatic aneurysms, n=32). A control group consisted of 14 kidney donors. Aortic walls were examined by immunohistochemistry and microscopy to detect inflammatory cells. More pronounced inflammatory changes and higher cytosol cytokine levels [IL6 (p<0.001), IL8 (p<0.0003) and TNFalpha (p<0.002)] were found in the walls of ruptured aneurysms than in the asymptomatic aneurysms. Immunohistochemically, most cells within the inflammatory infiltrates stained positively with the monoclonal antibody to the leucocyte common antigen (CD 45). The majority were of B-cell origin, which was demonstrated by positive staining with the monoclonal antibody L26 directed against the CD 20 antigen. These results show that an inflammatory process plays a significant role in patients with ruptured abdominal aortic aneurysms (AAA). A means of modifying the inflammatory process in the wall of AAAs might play an important role in preventing aneurysm rupture.

• MeSH
• aneurysma břišní aorty imunologie   komplikace   metabolismus   patologie   MeSH
• antigeny CD20 metabolismus   MeSH
• antigeny CD45 metabolismus   MeSH
• cytokiny analýza   MeSH
• interleukin-6 analýza   MeSH
• interleukin-8 analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky metabolismus   MeSH
• plazmatické buňky ultrastruktura   MeSH
• prasklé aneurysma chirurgie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• TNF-alfa analýza   MeSH
• tunica media patologie   ultrastruktura   MeSH
• zánět * imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• aneurysma břišní aorty metabolismus   MeSH
• biologické markery MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidové fragmenty krev   metabolismus   MeSH
• prokolagen krev   metabolismus   MeSH
• radioimunoanalýza MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH