scholarly journals Plasma Homocysteine Is Weakly Correlated with Plasma Endothelin and von Willebrand Factor but not with Endothelium-dependent Vasodilatation in Healthy Postmenopausal Women

1999 ◽  
Vol 45 (8) ◽  
pp. 1200-1205 ◽  
Author(s):  
Gerdien W de Valk-de Roo ◽  
Coen DA Stehouwer ◽  
Jan Lambert ◽  
Casper G Schalkwijk ◽  
Marius J van der Mooren ◽  
...  

Abstract Background: Hyperhomocysteinemia is an independent cardiovascular risk factor, possibly through the induction of endothelial dysfunction. The postmenopausal state is associated with increased plasma homocysteine. We examined whether increased homocysteine is associated with impaired endothelial function. Methods: Sixty-three hysterectomized but otherwise healthy postmenopausal women (54.8 ± 3.5 years) participated in this study. Fasting total plasma homocysteine (tHcy) was measured as free plus protein-bound homocysteine. Endothelial function was assessed by measuring plasma concentrations of the endothelium-derived proteins endothelin (ET), von Willebrand factor (vWF), and plasminogen activator inhibitor type 1 (PAI-1) as well as brachial artery flow-mediated, endothelium-dependent vasodilatation (FMD). Results: Plasma tHcy was 9.6 ± 2.5 μmol/L. After adjustment for possible confounders, a 1 μmol/L increase in tHcy was associated with an increase in ET of 0.08 ng/L (P = 0.045) and an increase in vWF of 4.2% (P = 0.05). No statistically significant association was present between tHcy and PAI-1 or FMD. Conclusions: Increased fasting homocysteine in postmenopausal women may impair some aspects of endothelial function. It is of clinical interest to study whether homocysteine lowering can improve endothelial function and thus cardiovascular morbidity and mortality in postmenopausal women.

1995 ◽  
Vol 74 (02) ◽  
pp. 626-630 ◽  
Author(s):  
A D Blann ◽  
M Dobrotova ◽  
P Kubisz ◽  
C N McCollum

SummaryTissue plasminogen activator antigen (tPA), plasminogen activator inhibitor antigen (PAI-1), soluble P-selectin and von Willebrand factor antigen (vWf) were measured by ELISA in 41 patients with peripheral vascular disease (PVD), 41 with ischaemic heart disease (IHD) and in 46 age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0002) and in patients with PVD (p = 0.0011) relative to the controls but levels did not differ between the two patients groups. Raised tPA found in both PVD (p = 0.0006) and IHD (p = 0.0061) compared to the controls also failed to differentiate the two groups of patients. Soluble P-selectin was also raised in both groups (p = 0.003 in IHD and p = 0.0102 in PVD) with no difference between the groups. There were no differences in levels of PAI-1 between the groups. In the subjects taken as a whole, there were significant Spearman’s correlations between tPA and vWf (r = 0.37, p <0.001), tPA and triglycerides (r = 0.38, p <0.001), tPA and P-selectin (r = 0.19, p = 0.032), vWf and age (r = 0.25, p = 0.005) and inversely between vWf and HDL (r = -0.25, p = 0.006). These data support the concept that increased levels of tPA may be important in atherosclerosis, and indicate that soluble P-selectin may be useful in further analysis of the role of platelets and the endothelial cell in this disease.


2009 ◽  
Vol 37 (3) ◽  
pp. 595-600 ◽  
Author(s):  
J Liu ◽  
N-L Sun ◽  
J Yang ◽  
J-H Huang

To compare the effects of losartan and atenolol on plasma fibrinolytic parameters and von Willebrand factor (vWF), Chinese subjects with mild-to-moderate hypertension were randomized to receive losartan (50 mg/day; n = 30) or atenolol (50 mg/day; n = 30) for 8 weeks. If target blood pressure (< 140/90 mmHg) was not achieved at week 4, hydrochlorothiazide (12.5 mg/day) was also administered. Plasma levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and vWF were determined at baseline and after treatment. Between-group baseline characteristics and blood pressure decrease were comparable. Losartan significantly reduced plasma PAI-1 and vWF and PAI-1/tPA ratio. Atenolol significantly increased plasma tPA, but PAI-1, vWF and PAI-1/tPA ratio were unchanged. In conclusion, losartan, but not atenolol improved the fibrinolytic system and reduced plasma vWF levels in Chinese hypertensives.


2016 ◽  
Vol 62 (5) ◽  
pp. 27-28
Author(s):  
Marina V. Grigoryan ◽  
Maria N. Ryabinina ◽  
Naida I. Bulaeva ◽  
Elena Z. Golukhova

Aim. The present study was designed to evaluate the prognostic value of platelet reactivity, initial level of inflammation markers and endothelial dysfunction, as well as CYP2C19*2 allele carriage in clinical outcome after percutaneous coronary interventions (PCI) in patients with stable coronary artery disease (SCAD) on dual antiplatelet therapy (DAPT).Methods. A prospective, single-center study included 94 patients with SCAD who underwent PCI with DES implantation, 20% had diabetes mellitus. Platelet reactivity was determined in all patients using light transmission aggregometry induced with 5μmol/L ADP (LTA-ADP) and VerifyNow before PCI, as well as CYP2C19 genotyping. In 74 patients were determined baseline levels of high-sensitivity C-reactive protein, soluble P-selectin, soluble CD40 ligand, highly sensitive IL-6, plasminogen activator inhibitor-1 levels and von Willebrand factor activity. Mean follow-up period was 28,2±15,5 months. Cumulative endpoint included major adverse cardiac event, stent thrombosis, angina recurrence or angiographically confirmed restenosis.Results. According to univariate regression analysis we revealed that diabetes mellitus [exp (B) 0,344 95% CI 0,118-1,004, p=0,049], PRU [exp (B) 1,009; 95% CI 1,002-1,017, p=0.01], number of stented arteries [exp (B) 4,00; 95% CI 1,475-10,848, p=0.01], number of implanted stents [exp (B) 3,672; 95% CI 1,366-9,872, p=0.01], baseline levels of PAI-1 [exp (B) 1,000, 95% CI 0,999-1,000, p=0.03] and von Willebrand activity [exp (B) 1,000, 95 1,000-1,000% CI, p=0.01]. The presence of CYP2C19*2 carriers revealed no significant impact on outcome after PCI. Using ROC-curve analysis to determine cutoff values for PRU was 202 (AUC 0,664; 95%CI 0,531-0,796, р=0,02), PAI-1 level - 75,95 ng/ml, (AUC 0,726, 95%CI 0,576-0,876, р=0,01), von Willebrand factor activity – 155,5% (AUC 0,724, 95%CI 0,561-0,887, р=0,01). Multivariate analysis revealed that concomitant diabetes mellitus, PRU ≥202, PAI-1 level ≥75.95 ng/ml, von Willebrand factor activity ≥155.15% are independent predictors of adverse cardiac events. Based on our findings we developed predictive models for risk stratifying of patients with CAD before PCI.Conclusions. Present study reveals following independent predictors of adverse cardiac events in patients with SCAD after PCI: concomitant diabetes mellitus, the value of PRU (≥202), the level of plasminogen activator inhibitor-1 (≥75.95 ng/ml) and von Willebrand factor activity (≥155.15%).


2001 ◽  
Vol 86 (09) ◽  
pp. 791-799 ◽  
Author(s):  
George Pancio ◽  
Arthur Moss ◽  
Vijay Kalaria ◽  
Victor Marder ◽  
Harvey Weiss ◽  
...  

SummaryDiabetes is an established risk factor for reinfarction and cardiac death in postinfarction patients. Since the underlying mechanism of diabetes-related risk is not fully understood we aimed to evaluate the association between lipids, thrombogenic factors and diabetes in postinfarction patients. The study population consisted of 1,045 post-infarction patients (846 non-diabetic, 125 non-insulin- and 74 insulin-requiring diabetics) with the following blood tests performed 2 months after an index myocardial infarction: lipoprotein (a), apolipoprotein-B, apolipoprotein-A, cholesterol, HDL cholesterol, triglycerides, insulin, von Willebrand factor (vWF), fibrinogen, factor VII, D-dimer, and plasminogen activator inhibitor (PAI-1). After adjustment for relevant clinical covariates, non-insulin-requiring diabetes was significantly (p <0.05) associated with elevated levels of (odd ratios per 1 log unit increase in parenthesis) vWF (1.74) and PAI-1 (1.42) whereas insulin requiring diabetes was associated with even more elevated levels of vWF (4.68), but not with increased levels of PAI-1. No significant differences in lipid levels were observed among three groups. In conclusion, increased level of von Willebrand factor is significantly and independently associated with diabetes in postinfarction patients, suggesting that endothelial damage is the primary mechanisms contributing to an increased occurrence of vascular and cardiac events in diabetic postinfarction patients.


2020 ◽  
Vol 59 (8) ◽  
pp. 3581-3590 ◽  
Author(s):  
Urban Alehagen ◽  
J. Alexander ◽  
J. Aaseth ◽  
A. Larsson ◽  
T. L. Lindahl

Abstract Purpose Endothelial dysfunction and inflammation are conditions which fuel atherosclerosis and ischaemic heart disease. We have previously reported reduced cardiovascular (CV) mortality following supplementation with selenium and coenzyme Q10 to 443 elderly individuals with low selenium status (mean 67 μg/L) for 4 years. Here, we wanted to evaluate a possible association between the supplementation and the plasma concentrations of the von Willebrand factor (vWf), and the plasminogen activator inhibitor-1 (PAI-1), as they, besides other functions, are also strongly associated with endothelial function. Methods In this sub-study, 308 individuals (active substance: 157, placebo: 151) were included. Blood samples were drawn after 6 and 36 months and vWf and PAI-1 were determined in plasma by ELISA. Changes in concentrations of the biomarkers were evaluated by the use of T tests, repeated measures of variance, and ANCOVA analyses. Results The active treatment group presented a lower level of vWf after 36 months compared with the placebo group (1.08 U/mL vs. 5.10 U/mL; p = 0.0007). The results were validated through the repeated measures of variance evaluation. The PAI-1 levels showed an equally significant decrease in the active group (26.2 ng/mL vs. 49.2 ng/mL; p = 0.0002) and were also validated through repeated measures of variance evaluation. Conclusion In this sub-study on elderly receiving selenium and coenzyme Q10, or placebo we found significantly lower levels of vWf and PAI-1 in the active treatment group as compared to the placebo group. We interpret this as a better endothelial function because of the intervention, which accords with a previous finding of reduced CV mortality.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1492-1492
Author(s):  
Darintr Sosothikul ◽  
Panya Seksarn ◽  
Sureeporn Pongsawaluk ◽  
Jeanne M. Lusher

Abstract Dengue virus causes febrile illnesses: Dengue Fever (DF) and less frequently a life-threatening illness, Dengue Hemorrhagic Fever (DHF). The pathophysiology of hemostatic defect in dengue infection is thought to relate to the direct effect of virus or cytokines on endothelial activation. To study the state of endothelial activation during dengue infection, we measured plasma levels of von Willebrand factor antigen (vWF:Ag), vWF-collagen binding assay (vWF:CBA), and ADAMTS 13 activity in 42 children (20 with DF and 22 with DHF) during 3 phases of illness: febrile, toxic, and convalescent phase. 38 healthy children comprised as controls. Our data shows that both VWF:Ag and vWF:CBA levels were significantly higher in dengue patients (p ≤ 0.001 in both DF and DHF patients) versus controls. DHF patients had significantly higher of VWF: Ag (p = 0.01, versus DF). ADAMTS 13 activity levels were significantly decreased only in DHF patients during 3 phases of the illness (febrile; mean 78%; p = 0.016, toxic; mean 68%; p<0.001 and convalescent; mean 69%; p<0.001 compared to mean 104% of the controls). Compared to DF patients, DHF patients had significantly lower plasma concentrations of ADAMTS 13 activity during the febrile, toxic and convalescent phase (p = 0.039, p = 0.002 and p =0.003, respectively). Endothelial cell activation is a hallmark of dengue infection especially in DHF patients; indicated by a significant rise in VWF:Ag and vWF:CBA and a reciprocal decline in ADAMTS 13 activity.


2013 ◽  
Vol 5 (1) ◽  
pp. e2013046 ◽  
Author(s):  
Antoine Rauch ◽  
Peter Lenting

Von Willebrand factor (VWF) is a large multimeric protein, the function of which has been demonstrated to be pivotal to the haemostatic system. Indeed, quantitative and/or qualitative abnormalities of VWF are associated with the bleeding disorder Von Willebrand disease (VWD). Moreover, increased plasma concentrations of VWF have been linked to an increased risk for thrombotic complications. In the previous decades, many studies have contributed to our understanding of how VWF is connected to the haemostatic system, particularly with regard to structure-function relationships. Interactive sites for important ligands of VWF (such as factor VIII, collagen, glycoprotein Iba, integrin aIIbb3 and protease ADAMTS13) have been identified, and mutagenesis studies have confirmed the physiological relevance of the interactions between VWF and these ligands.  However, we have also become aware that VWF has a more versatile character than previously thought, given its potential role in various non-hemostatic processes, like intimal thickening, tumor cell apoptosis and inflammatory processes. In the presence review, a summary of our knowledge on VWF structure-function relationships is provided in the context of the "classical" haemostatic task of VWF and in perspective of pathological processes beyond haemostasis.


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