The effect of multi-factorial intervention on plasma von Willebrand factor, soluble E-selectin and tissue factor in diabetes mellitus: implications for atherosclerotic vascular disease

SummaryVon Willebrand factor (VWF) is a multifunctional plasma protein that plays a prominent role in haemostasis. In endothelial cells, processing of its precursor pro-VWF results in the formation of two large polypeptides, mature VWF and a propeptide. These proteins are co-secreted on an equimolar basis but are cleared from the circulation at different rates. VWF levels are frequently elevated in response to vascular disorders. Similarly, propeptide levels are increased under these conditions, although primarily in fulminant vascular disease, such as thrombotic thrombocytopenic purpura and septicemia. In chronic vascular disease, e.g. diabetes or peripheral vascular disease, propeptide levels are much less elevated. The differential response of VWF and propeptide levels to vascular disease could provide a means to assess the extent and time course of endothelial cell activation. After secretion, the propeptide may play a role in modulating cellular adhesion processes. Thus, enhanced propeptide secretion seems not to be of merely diagnostic significance.

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Transcriptional Expression of Tissue Factor Pathway Inhibitor, Thrombomodulin and von Willebrand Factor in Normal Human Tissues

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614327 ◽

1999 ◽

Vol 82 (09) ◽

pp. 1047-1052 ◽

Cited By ~ 42

Author(s):

M. N. Kuppuswamy ◽

A. N. Manepalli ◽

S. P. Bajaj ◽

M. S. Bajaj

Keyword(s):

Skeletal Muscle ◽

Tissue Factor ◽

Von Willebrand Factor ◽

Tissue Factor Pathway Inhibitor ◽

Northern Blotting ◽

Transcriptional Expression ◽

Microvascular Endothelium ◽

Tissue Factor Pathway ◽

Von Willebrand ◽

Willebrand Factor

SummaryUnder normal physiologic conditions, tissue factor pathway inhibitor (TFPI) is synthesized primarily by the microvascular endothelium. Using Northern blotting, we studied its transcriptional expression in different organs and compared it with the expression of two other endothelial specific proteins, namely thrombomodulin (TM) and von Willebrand factor (vWF). The order of mRNA expression for each protein was: TFPI–placenta>lung>liver>kidney>heart>skeletal muscle≥pancreas>brain; TM–heart>pancreas>lung>skeletal muscle>kidney≥liver>placenta>brain; and vWF–heart>skeletal muscle>pancreas>lung≥kidney>placenta>brain>liver. Notably, heart expressed TM and vWF mRNA in large amounts and only small amounts of TFPI whereas lung expressed all three mRNAs in significant amounts. Placenta, on the contrary, expressed large amounts of TFPI but only small amounts of TM and vWF mRNAs. Brain by this technique was found to express undetectable amounts of TFPI and TM mRNAs but small amounts of vWF mRNA. The expression of TFPI mRNA in the brain was however detected by RT/PCR and the antigen was localized to the endothelium of microvessels as well as to the astrocytes and oligodendrocytes. Since ultimate expression of proteins is linked to the expression of their mRNAs, our data support a concept that vascular endothelium is made up of phenotypically diverse groups of cells and that endothelial cells of different vascular beds express specific sets of genes that enable them to carry out tissue-specific functions. Importantly, since astrocytes are known to express tissue factor, the TFPI expression by these cells may control coagulation in their microenvironment and their response to injury and inflammation.

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Von Willebrand Factor Levelsand Control glycemic Type 2 Diabetes Mellitus Patients

Proceedings of the International Conference of Science, Technology, Engineering, Environmental and Ramification Researches ◽

10.5220/0010067504030406 ◽

2018 ◽

Author(s):

. Rusdiana ◽

Maya Savira ◽

Sry Suryani Widjaja ◽

Muhammad Syahputra

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Von Willebrand Factor ◽

Von Willebrand ◽

Willebrand Factor

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Tissue Factor Firmly Immobilized on Surfaces Promotes Platelet Adhesion and Fibrin Formation in Studies with Circulating Human Blood: Importance of Shear Rate Conditions and FVIIa.

Blood ◽

10.1182/blood.v108.11.3925.3925 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3925-3925

Author(s):

Raul Tonda ◽

Irene Lopez-Vilchez ◽

Ana M. Galan ◽

Fulgencio Navalon ◽

Marcos Pino ◽

...

Keyword(s):

Tissue Factor ◽

Von Willebrand Factor ◽

Platelet Adhesion ◽

Statistical Significance ◽

Low Molecular Weight ◽

Shear Rates ◽

Fibrin Formation ◽

Closure Time ◽

Von Willebrand ◽

Willebrand Factor

Abstract While procoagulant activity of tissue factor (TF) has been widely investigated, its possible proadhesive properties towards platelets have not been studied in detail. We explored the interaction of platelets with human TF (hTF) firmly attached to a surface using anticoagulated blood with low molecular weight heparin (20 U/ml) at different shear rates. For studies at 250 s−1 and 600 s−1, TF adsorbed on a synthetic surface was exposed to circulating blood in flat perfusion devices. Deposition of platelets and fibrin formation were evaluated by morphometric, immunocytochemical and ultrastructural methods. For experiments at 5000 s−1, we used the PFA-100™ with experimental cartridges with collagen or collagen-hTF. Effect of rFVIIa was assessed in all experimental settings. Prothrombin fragment F1+2 levels were also measured. At 250 and 600 s−1 platelet interaction was 19.84±1.33% and 26.12±3.42% of the total surface respectively. Our inmunocytochemical results suggest that von Willebrand factor could mediate these interactions. Fibrin formation was significantly higher at 250 s−1 than at 600 s−1 (p<0.05). FVIIa tended to increase platelet deposition without reaching statistical significance, and raised fibrin formation and thrombin generation (p<0.05). Our At 5000 s−1, closure times in the PFA-100 were significantly shortened in the presence of hTF (154.09 ±14.69 s vs 191.45± 16.09 s with collagen alone; p<0.05). Addition of rFVIIa did not result in a further reduction of closure time. Our studies demonstrate that hTF is reactive for platelets. von Willebrand factor could mediate these interactions. Recombinant FVIIa enhances the procoagulant action of hTF at low and intermediate shear rates, but has no impact on the hemostatic performance at very elevated shear rates.

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Association of Quantitative and Qualitative Abnormalities of Von Willebrand Factor and Risk of Death In Hemodialysis Patients

Blood ◽

10.1182/blood.v116.21.2217.2217 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2217-2217

Author(s):

Rachel Holden ◽

Angie Tuttle ◽

Francis MacLeod ◽

Toni Burbidge ◽

Carol Hegadorn ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Vascular Disease ◽

Von Willebrand Factor ◽

Functional Activity ◽

Conflicts Of Interest ◽

Proteolytic Processing ◽

Risk Of Death ◽

Von Willebrand ◽

Willebrand Factor

Abstract Abstract 2217 In order to evaluate the possible role of abnormalities of von Willebrand factor in the hemostatic defects seen in indivdiuals with chronic kidney disease (CKD), a cohort study was performed evaluating pre- and post-dialysis levels of von Willebrand factor (VWF), VWF multimer profiles and levels of its cleaving protease, ADAMTS-13. There were 57 subjects (31 males, 26 females) enrolled with CKD with a mean age of 75 years (range 60 – 90). Subjects with known vascular disease were recruited; 49 (86%) had documented ischemic heart disease, 16 (29%) had cerebrovascular disease and 17 (31%) had peripheral vascular disease. A little over half had diabetes mellitus (30 subjects or 54%), 37 (67%) were on antiplatelet therapy and 7 (13%) were chronically anticoagulated with warfarin. Blood samples were drawn immediately pre- and again post-dialysis and all results were compared with a group of age-matched normal controls (Table 1). As has been previously reported, VWF antigen levels (VWF:Ag) and VWF functional activity as measured by the ristocetin cofactor assay (VWF:RCo) were higher in the pre-dialysis samples compared with controls, and both levels were increased even further following dialysis. Additionally, the percentage of high molecular weight VWF multimers (% HMWM) were significantly increased in the pre-dialysis samples compared with controls. This is a novel finding, and the level of % HMWM seen in the subjects is similar to what has been reported in individuals with Thrombotic Thrombocytopenic Purpura (TTP). This difference decreased following dialysis, potentially due to the effect of shear stress on VWF and the resultant proteolytic processing, however still remained significantly higher when compared with controls. ADAMTS-13 functional activity was lower in the subjects compared with controls, providing a possibly explanation for the increase in % HMWM. IL-6 levels are higher in subjects compared with controls. IL-6, which is an inflammatory cytokine known to be increased in patients with CKD, has been previously reported as a marker of inactivation of ADAMTS-13. Two years after enrollment, follow up of the subjects revealed that 22 had died, 17 from documented cardiovascular events. Higher VWF levels at the time of enrollment significantly correlated with risk of death (p=0.041) during the study period. The increase in % HMWM suggests that a “TTP-like phenotype” may also be playing a role. Taken together, these data suggest that both quantitative and qualitative abnormalities of VWF contribute to the risk of thrombotic death in chronic kidney disease. Disclosures: No relevant conflicts of interest to declare.

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