Sheep anti Human Tissue Factor Pathway Inhibitor polyclonal antibody

OBJECTIVES: We aimed to associate a coronary artery disease (CAD) presence and severity with endothelial dysfunction (ED), carotid intima media thickness (CIMT) and Tissue Factor Pathway Inhibitor (TFPI). BACKGROUND: ED has a central role in atherosclerosis. CIMT and TFPI activity are also related with atherosclerosis and CAD. METHODS: In our prospective observational study, 50 patients had CAD and 30 had normal coronary arteries. Endothelial function was evaluated by endothelium-dependent flow-mediated dilatation (FMD) and nitroglycerinemediated dilatation (NMD) measurements. CIMT and Serum TFPI levels were also measured. RESULTS: TFPI was a statistically significant determinant between the two groups with an increased level in CAD (+) group (84.9 +/- 19.3 vs 70.2 +/- 14.7, p = 0.001). There was a positive correlation between CIMT and Gensini (r = 0.34, p = 0.014). There was a strong negative correlation between Gensini and FMD-NMD, statistically significant (FMD: r =-0.715, p < 0.001; NMD: r = -0.718, p < 0.001). CONCLUSION: We observed that ED, increased CIMT and TFPI levels were associated with CAD. Additionally, increased CIMT measurements and decreased FMD and NMD values had a positive correlation with GSS (Tab. 4, Fig. 6, Ref. 50). Text in PDF www.elis.sk.

Epigenetic modifications are important early events during carcinogenesis. In particular, hypermethylation of CpG islands in the promoter region of tumor suppressor genes is a well-known mechanism of gene silencing that contributes to cancer development and progression. Tissue factor pathway inhibitor 2 (TFPI-2) is a tumor suppressor involved in invasiveness inhibition. Although TFPI-2 transcriptional silencing, through promoter hypermethylation, has been widely reported in several human malignancies, it has never been explored in lymphoma. In the present study TFPI-2 methylation and gene expression have been investigated in canine Diffuse Large B-cell lymphomas (cDLBCL). The methylation level of 23 CpGs located within the TFPI-2 promoter was investigated by bisulfite-specific PCR and next generation amplicon deep sequencing (GS Junior 454, Roche) in 22 cDLBCLs and 9 controls. For the same specimens, TFPI-2 gene expression was assessed by means of Real-time RT-PCR. Sequence analysis clearly demonstrated that TFPI2 is frequently hypermethylated in cDLBCL. Hypermethylation of the TFPI-2 promoter was found in 77% of DLBCLs ( 17 out of 22) and in one normal lymph node. Globally, dogs with DLBCL showed a mean methylation level significantly increased compared to controls (p<0.01) and analysis of hypermethylation by site identified 19 loci out of 23 ( 82%) with mean methylation levels from 2- to 120-fold higher in cDLBCL. Gene expression analysis confirmed a significant down-regulation of TFPI-2 ( p<0.05) in DLBCLs compared with normal lymph nodes, suggesting that TFPI-2 hypermethylation negatively regulates its transcription. In addition, a significant positive correlation ( p<0.01) was found between TFPI-2 methylation levels and age providing the first indication of age-associated epigenetic modifications in canine DLBCL. To conclude, our findings demonstrated that epigenetic dysregulation of TFPI-2, leading to its reduced expression, is frequently detected in canine DLBCL. In the next future, the aberrant TFPI-2 promoter hypermethylation may be considered in association with prognosis and therapy.