scholarly journals Von Willebrand Factor Multimers and the Relaxation Response: A One-Year Study

Entropy ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. 447
Author(s):  
Carlo Dal Lin ◽  
Laura Acquasaliente ◽  
Sabino Iliceto ◽  
Vincenzo De Filippis ◽  
Giuseppe Vitiello ◽  
...  

Background and aim: Mental stress represents a pivotal factor in cardiovascular diseases. The mechanism by which stress produces its deleterious ischemic effects is still under study but some of the most explored pathways are inflammation, endothelial function and balancing of the thrombotic state. In this scenario, von Willebrand factor (vWF) is a plasma glycoprotein best known for its crucial hemostatic role, also acting as key regulatory element of inflammation, being released by the activated vascular endothelium. Antistress techniques seem to be able to slow down inflammation. As we have recently verified how the practice of the Relaxation Response (RR), which counteracts psychological stress, causes favorable changes in some inflammatory genes’ expressions, neurotransmitters, hormones, cytokines and inflammatory circulating microRNAs with coronary endothelial function improvement, we aimed to verify a possible change even in serum levels of vWF. Experimental procedure: We measured vWF multimers and the total protein carbonyl contents in the sera of 90 patients with ischemic heart disease (and 30 healthy controls) immediately before and after an RR session, three times (baseline, 6 months, 12 months), during a one-year follow-up study. Results: According to our data, large vWF multimers decrease during the RR, as does the plasma total carbonyl content. Conclusion: vWF levels seem to vary rapidly between anti-inflammatory and antithrombotic behaviors dependent on psychological activity, leading to relaxation and also possibly changes in its quaternary structure.

Biochemistry ◽  
1985 ◽  
Vol 24 (16) ◽  
pp. 4468-4475 ◽  
Author(s):  
Joseph Loscalzo ◽  
Michael Fisch ◽  
Robert I. Handin

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4028-4028
Author(s):  
Hong I. Tarng ◽  
Lynne Taylor ◽  
Barbara A. Konkle

Abstract A number of inherited and acquired factors modulate von Willebrand factor antigen (VWF:Ag) levels, including blood type, race, activity and stress level, thyroid hormone status, and, in women, time in menstrual cycle. In reported studies a positive correlation between VWF:Ag and/or factor VIII levels and age has been demonstrated, with an increase of 5 – 6 IU/dL per decade (Conlan MG et al, 1993; Kamphuisen PW et al, 1998). Those studies have primarily assessed VWF and factor VIII as risk factors for ischemic heart disease, cerebrovascular disease, and venous thromboembolism. None of the subjects had von Willebrand disease (VWD). Their VWF:Ag levels were in the higher normal or elevated range. The purpose of this study was to determine whether there is a relationship between age and VWF:Ag level in patients with Type 1 VWD. We collected the data from 36 patients who were diagnosed with type 1 VWD and followed at the Penn Comprehensive Hemophilia and Thrombosis Program up to a period of 13 years (See Table 1 below). For each patient, date of birth, VWF:Ag levels with corresponding test dates were collected by reviewing the medical histories and the lab results. Test results obtained during pregnancy, DDAVP testing, or during prophylaxis or therapy for bleeding control were excluded. One year was set as the observation period, so the adjacent VWF:Ag levels that were tested less than one year were excluded from the dataset. When two test results were available on a patient within a one-year period, the lower test result was used. To investigate whether there was a relationship between VWF:Ag levels and age, cross-sectional analyses (across each visit) and longitudinal analyses were performed using scatter plots, Spearman and Pearson correlations, and regression analysis. No significant increase in VWF:Ag levels with age was demonstrated. The fact that we did not find an increase in VWF:Ag levels over time in our patients could be due to the relatively small number of patients studied or could reflect a subtype of VWD, due to our selection criteria. Only patients with abnormal values were included. Some patients have a prior diagnosis of VWD and bleeding symptoms, but have normal values when tested. Since these patients are adults, this may be due, at least in part, to an age-related increase. Type 1 VWD may occur secondary to decreased VWF synthesis and/or clearance. It is possible that age-related effects on VWF levels will differ depending on the underlying factor(s) resulting in a lower VWF level. Further studies correlating a patient’s values longitudinally with the underlying pathophysiology of their disease would aid in our understanding of their bleeding risks over time. Patient # Age at Last Visit, range (mean) Females (%) Race % (Cauc/AA/Other) VWF:Ag mean 36 17–70 (34) 89 78/19/3 49%


2007 ◽  
Vol 13 (4) ◽  
pp. 256-261
Author(s):  
N. YU. Klimenko ◽  
N. V. Drobotya ◽  
A. A. Kastanyan ◽  
V. V. Kaltykova ◽  
E. Sh. Guseynova

A study of daily blood pressure (BP) dynamics, functional endothelial condition at hypertensive patients in combination with tuberculosis of various localization and estimation of an opportunity of correction of the revealed disturbances during 12-week therapy by the fixed combination of perindopril and indapamide - noliprel-forte (Servier, France) were performed. During research more expressed endothelial dysfunction at hypertensive patients, proceeding on a background of tubercular process in comparison with patients with isolated arterial hypertension was revealed. Therapy by noliprel-forte provided the reliable 24-hour control of BP level, which was accompanied by endothelial function normalization that was shown by improvement of a endothelium-dependent vasodilatation and decrease of a von Willebrand factor level. .


Author(s):  
Ya. V. Sirman ◽  
I. V. Savytskyi

One of the main diabetes complications that can lead to the disability of patients is diabetic retinopathy. The purpose of the study was to investigate endothelial dysfunction markers in modelled diabetic retinopathy. Material and methods. The experiment was conducted on male rats of the Wistar line, weighing 180-220 grams, up to 3 months of age (inclusive). During the experiment, the animals were divided into two groups. The 1st group included 20 intact animals; the 2nd group had 60 animals with modelled diabetes mellitus and non-proliferative diabetic retinopathy. Results and discussion. Having studied endothelial nitric oxide synthase, we have found out significant differences (p <0.001) when comparing the findings obtained in the 2nd group with the findings of the intact animals. The 2nd group rats were simulated with diabetic retinopathy without following correction. We also observed the decreasing dynamics of this index. For a more detailed study of the functional state of the endothelium and its disruption, we selected the von Willebrand factor, which is one of the common markers showing the damage to the functional state of the endothelium. In the group with simulated pathology, the level of the investigated marker increased compared with intact animals (p <0.001). There was an increase in endothelin-1 level (p <0.001) in the laboratory rats with modelled diabetic retinopathy. Conclusion. The study results have proven that our experimental model of diabetes mellitus and one of its complications, diabetic retinopathy is accompanied by the development of endothelial dysfunction. There has been found as increase in the von Willebrand factor in the modelled pathological process. We have detected an increase in endothelin-1, a marker of vasoconstriction and endothelial dysfunction, 30 days since the beginning of the experiment. Inhibition of endothelial NO synthase activity indicates an impairment of the physiological NO synthesis.


Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3468-3478 ◽  
Author(s):  
JG White ◽  
MD Krumwiede ◽  
D Cocking-Johnson ◽  
GH Rao ◽  
G Escolar

The present study has evaluated the hypothesis stating that glycoprotein (GP) Ib/IX, the receptor for von Willebrand factor (vWF), is downregulated and cleared from exposed surfaces to channels of the open canalicular system (OCS) on platelets activated by thrombin in suspension. Cryosections of resting and thrombin-activated platelets fixed at intervals of 1 to 30 minutes after stimulation by thrombin and stained with antiglycocalicin antibody and protein A gold showed no decrease in the density of GPIb/IX receptors on the platelet surface or increase on linings of the OCS at any interval after stimulation by thrombin. Thin sections of platelets exposed to thrombin in suspension followed by settling onto a plastic chamber for intervals of 1 to 30 minutes revealed retention of GPIb/IX receptors on exposed surfaces detected by vWF, anti-vWF, and protein A gold throughout the 30-minute period of study. Results of this investigation indicate that GPIb/IX receptors remain on the surface of platelets activated by thrombin in suspension, are not cleared to the OCS, and retain the ability to bind vWF for at least 30 minutes.


2021 ◽  
Author(s):  
Goetz Hermann ◽  
Andrea Blum ◽  
Daniel Bolliger ◽  
Rita Achermann ◽  
Anna Estermann ◽  
...  

Abstract Introduction: Von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia. To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss, despite being widely used in clinical practice. The Basel Will-Plate study will investigate the impact of timely administration of balanced vWF (1:1 vWF and FVIII) in addition to platelet transfusion on need for blood and coagulation factor transfusion in patients admitted to the intensive care unit (ICU) who suffer from severe bleeding. The study hypothesis is based on the assumption that by adding balanced vWF to platelets will reduce the overall need of transfusion of blood products compared to transfusion of platelets alone. Methods and Analysis: The Will-Plate study is an investigator-initiated, single-centre, double-blinded randomised controlled clinical trial in 120 critically ill patients needing platelet transfusion. The primary outcome measure will be the number of fresh frozen plasma (FFP) and red blood cell (RBC) transfusions according to groups. Secondary outcome measures include number of platelet concentrates transfused within the first 48 h after treatment of study medication, quantity of blood loss in the first 48 hours after treatment with the study medication, length of stay in ICU and hospital, number of revision surgeries for haemorrhage control, ICU mortality, hospital mortality, 30-day mortality and one-year mortality. Patients will be followed after 30 days and 1 year for activities of daily living and mortality assessment. Sample size was calculated to detect a 50% reduction of the number of blood products subsequently transfused within two days in patients with Wilate® compared to placebo. Ethics and dissemination: This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) as well as all national legal and regulatory requirements. Study results will be presented in international conferences and published in a peer-reviewed journal. Trials registration: ClinicalTrials.gov Identifier: NCT04555785 Protocol version: Clinical Study Protocol Version 2, 01.11.2020


2015 ◽  
Vol 113 (03) ◽  
pp. 577-584 ◽  
Author(s):  
Michelle A. Sonneveld ◽  
Jin Cheng ◽  
Rohit Oemrawsingh ◽  
Moniek P. M. de Maat ◽  
Isabella Kardys ◽  
...  

SummaryHigh von Willebrand factor (VWF) plasma levels are associated with an increased risk of coronary artery disease. It has been suggested that the increase of VWF levels is partly due to endothelial dysfunction and atherosclerosis. Our aim was to investigate the association between coronary plaque burden, the presence of high-risk coronary lesions as measured by intravascular ultrasound virtual histology (IVUS-VH) and VWF levels. In addition, we studied the association between VWF levels and one-year cardiovascular outcome. Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) (n= 318) or stable angina pectoris (SAP) (n= 263). Arterial blood was sampled prior to the coronary angiography. VWF antigen (VWF:Ag) levels were measured using ELISA (n= 577). Patients with ACS had significantly higher VWF:Ag levels than SAP patients (median 1.73 IU/ml [IQR 1.27–2.31] vs 1.26 IU/ml [0.93–1.63], p < 0.001). High coronary plaque burden was associated with higher VWF:Ag levels (β= 0.12, p=0.027) in SAP patients, but not in ACS patients. In ACS patients, VWF:Ag levels were associated with 1-year MACE (HR 4.14 per SD increase of lnVWF:Ag, 95 % CI 1.47–11.6), whereas in SAP patients VWF:Ag levels predicted 1-year all-cause death and hospitalisation for ACS (HR 7.07 95 % CI 1.40–35.6). In conclusion, coronary plaque burden was associated with VWF:Ag levels in SAP patients undergoing coronary angiography. In ACS and SAP patients, high VWF levels are predictive of adverse cardiovascular outcome and death during one-year follow-up.


Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1247-1258 ◽  
Author(s):  
Jean-Luc Schwachtgen ◽  
Jacques E. Remacle ◽  
Nathalie Janel ◽  
Reginald Brys ◽  
Danny Huylebroeck ◽  
...  

The negative regulation of transcription of the human von Willebrand factor (vWF) gene was investigated in human umbilical vein endothelial cells (HUVECs) and HeLa cells. A fragment spanning −89 to +244 nucleotides (nt), containing the first exon, is active in HUVECs only but not in HeLa cells. The activity of this promoter is sharply reduced by mutagenesis of the GATA binding site at +221. Extension of the upstream sequences from nt −89 to −142 and to −496 results in progressive reduction of the activity of the −89 to +244 promoter identifying a negative regulatory element between nt −142 and −89. A factor present in nuclear extracts from endothelial and nonendothelial cells binds to an AT-rich sequence located between nt −133 and −125. Mutagenesis of the AT-rich sequence interferes with nuclear protein binding and restores the activity of the −142 to +244 fragment to the level of the −89 to +244 promoter. Binding of the nuclear protein to the vWF AT-rich sequence in mobility shift assays is inhibited by competition with a consensus Oct-1 binding site and with a silencer octamer-like sequence from the vascular cell adhesion molecule-1 (VCAM-1) promoter. Subsequent supershift experiments identified Oct-1 as the transcription factor that binds to vWF and VCAM-1 silencer elements. These results indicate that Oct-1 acts as a transcriptional repressor of promoters of genes expressed in endothelial cells.© 1998 by The American Society of Hematology.


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