Dysregulations of Key Regulators of Angiogenesis and Inflammation in Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a chronic vascular disease caused by localized weakening and broadening of the abdominal aorta. AAA is a clearly underdiagnosed disease and is burdened with a high mortality rate (65-85%) from AAA rupture. Studies indicate that abnormal regulation of angiogenesis and inflammation contributes to progression and onset of this disease; however, dysregulations in the molecular pathways associated with this disease are not yet fully explained. Therefore, in our study, we aimed to identify dysregulations in the key regulators of angiogenesis and inflammation in patients with AAA in peripheral blood mononuclear cells (using qPCR) and plasma samples (using ELISA). Expression levels of ANGPT1, CXCL8, PDGFA, TGFB1, VEGFB, and VEGFC and plasma levels of TGF-alpha, TGF-beta 1, VEGF-A, and VEGF-C were found to be significantly altered in the AAA group compared to the control subjects without AAA. Associations between analyzed factors and risk factors or biochemical parameters were also explored. Any of the analyzed factors was associated with the size of the aneurysm. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors potentially involved in AAA formation, giving new insight into the molecular pathways involved in the development of this disease and providing candidates for biomarkers that could serve as diagnostic or therapeutic targets.

Antioxidant Potential of Diosmin and Diosmetin against Oxidative Stress in Endothelial Cells.

Phlebotropic flavonoids, including diosmin and its aglycone diosmetin, are natural polyphenols widely used in the prevention and treatment of chronic venous insufficiency (CVI). As oxidative stress plays an important role in the development of pathophysiology of the cardiovascular system, the study aimed to investigate the protective effects of diosmin and diosmetin on hydrogen peroxide (H2O2)-induced oxidative stress in endothelial cells. The cells were pretreated with different concentrations of the flavonoid prior to the H2O2 exposure. The cell viability, the level of intracellular reactive oxygen species (ROS), the activity of cellular antioxidant enzymes-including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase GPx-and the malondialdehyde (MDA) level were assessed. It was found that the H2O2-induced oxidative stress was ameliorated by diosmin/diosmetin in a concentration-dependent manner. The flavonoids restored the activity of cellular antioxidant enzymes and lowered the MDA level upregulated by the H2O2 exposure. These results indicate that diosmin and diosmetin may prevent oxidative stress in endothelial cells; therefore, they may protect against the development and progression of oxidative-stress-related disorders.

Immunomodelling Characteristics of Mature Dendritic Cells Stimulated by Colon Cancer Cells Lysates.

UNLABELLED: Application of cells with high TAA (tumor associated antigen) presentation potential seems to be crucial in neoplasia immunotherapy. Such feature is distributed in dendritic cells, which present peptides from processed TAA - MHC molecules complex to the T cells of a host. The aim of the study was to assess the influence of colon neoplasia tissue lysate on functioning of generated autologous DC's in the field of autologous CD4+ lymphocytes immunological response towards Th1/Th2 under in vitro environment together with comparison and assessment of DCs' immunosuppressive properties acquired from patients with colon cancer. MATERIAL AND METHODS: The population of this study consisted of 16 healthy- controls, 36colon cancer patients. Blood samples were collected 24h before planned surgery and preventive antibiotic therapy. Neoplastic tissue sample, was digested for cell lysates preparation. DC's generation from PBMC was carried out in standard conditionsand medium enriched with rhGM-CSF and rhIL-4. Mature DC`s and cocultured autologous CD4 lymphocytes immunophenotype assessment was analyzed with flow cytometer. Intracellular and culture medium cytokines concentration was analyzed with ELISA and FACS method. RESULTS: DC`s generated from colon cancer patients stimulated with lysates presented greater maturity, lower expression of CD206 antigen, significantly higher expression of HLA-DR, CD208 and CD209 and high intracellular expression of IL-12, compared to non-stimulated cells. CONCLUSIONS: The neoplastic tissue in vivo produces a number of substances having an unfavorable effect on immune system, our results suggests using lysates as good dendritic cells stimulators that possibly could have application in colon cancer immunotherapy.

Selected factors of fibrinolysis in the Buerger's disease.

UNLABELLED: Thrombangiitis obliterans (TAO marked by coexistence of thrombotic and inflammatory changes of neurovascular tract has evoked a considerable dispute concerning pathogenesis of this disease. The aim of the study was to define the level of activation of fibirinolitic system in course of TAO disease by means of determination its basic constituents as well as to examine the essence of level of fibrinolysis disorders in pathogenesis and development of this disease. MATERIAL AND METHODS: Fifty patients with thrombangiitis obliterans (TAO), 30 patients with peripheral occlusive disease - PAOD (ASO) and 20 healthy volunteers (K) have been subjected to the examination. We determined the activity some factors of fibrinolysis: t-PA, PAI-1, PAP, plasminogen, α2-antiplasminogen, D-dimmer as well as euglobulin lysis time. The analysis comprised 7 features and 8 factors of variability: a membership to a group of patients, sex, age, smoking, aggravation of the disease within last 3 months, occurrence of Raynaud's symptom, a degree of ischemia according to Fontaine, time the disease lasted. RESULTS: The significant differences between the average were checked by means of t-Student test or variance analysis (ANOVA) and co-relation rate r (Pearson). We concluded that the average value of PAI-1 in the group TAO was significantly higher than in comparison with ASO group. The increased values were revealed in case of 76 % of patients. The euglobulin lysis time was vitally extended in case of 60% of patients in ASO group. In all three groups higher levels of α2-antiplasmin were detected in case of elderly patients compared to the younger ones. CONCLUSIONS: The obtained results allow us to ascertain the state of potentially weakened fibrinolysis in case of patients with Buerger's disease as well as with PAOD.