Both these proteins are present on only mature WPBs, and this rab/effector complex appears to anchor these WPBs to peripheral actin. Depletion of either the Rab or its effector results in a loss of peripheral WPB localization, and this destabilization is coupled with an increase in both

basal and stimulated secretion. The VWF released from Rab27a-depleted cells is less multimerized, and the VWF strings seen under flow AG-881 mw are shorter. Our results indicate that this Rab/effector complex controls peripheral distribution and prevents release of incompletely processed WPB content. (Blood. 2009;113:5010-5018)”
“The invasion of monocytes into the subendothelium space plays an important role in the early stage of atherosclerosis. Cilostazol, a specific phosphodiesterase type III (PDE3) inhibitor, has been shown to exhibit anti-atherosclerotic effect. The present study aimed to investigate the modulating effects of cilostazol on monocyte invasion and the gene expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1. We found that PMA significantly increased the invasive ability and the MMP-9 activity of THP-1 cells, as analyzed by matrix invasion assay and gelatin zymography, respectively. The increased expression of MMP-9 was demonstrated at both

the RNA and protein levels by RT/real-time PCR and western blot analysis. These changes were markedly inhibited by cilostazol in a dose-dependent CHIR-99021 inhibitor manner, which also could be observed when cAMP analog was used. On the contrary, the expression of TIMP-1, an inhibitor of MMP-9, was significantly upregulated by cilostazol dose dependently at both the RNA and protein levels. Reverse zymography further confirmed the increase of TIMP-1 activity after cilostazol treatment. The increase of TIMP-1 by cilostazol, however, was not cAMP-dependent. Cilostazol reduced the

MMP-9 promoter activity and suppressed the nuclear translocation of NF-kappa GW4869 chemical structure B, indicating that the inhibitory effect of cilostazol is at the transcriptional level. In conclusion, the present study provides an additional mechanism underlying the anti-atherosclerotic effect of cilostazol by inhibiting the monocyte invasion and modulating the gene expressions of MMP-9 and TIMP-1 in monocytes upon differentiating to macrophages. (C) 2011 Elsevier B.V. All rights reserved.”
“Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil.