von Willebrand factor, endothelial

dysfunction, and cardiovascular disease

Author: VISCHER, U. M.

Source: Journal of Thrombosis and Haemostasis, Volume 4, Number 6, June 2006 , pp.
1186-1193(8)

Abstract:

von Willebrand factor (VWF), a glycoprotein involved in arterial thrombus formation, is

released into the circulation by secretion from endothelial cells. Plasma VWF levels are
determined by genetic factors including ABO blood groups and VWF mutations, and by
non-genetic factors including aging, impaired nitric oxide production, inflammation, free
radical production and diabetes. Plasma VWF levels have been proposed as a risk factor
for cardiovascular events. Although they are only weakly associated with the risk of
coronary heart disease (CHD) in the general population, they are a more promising CHD
risk factor in high-risk populations with previous cardiovascular events, diabetes or old
age. However, is it still unclear whether VWF levels directly determine the rate and
severity of arterial thrombus formation or whether they merely reflect alteration in other
endothelial functions. The future status of VWF levels as a cardiovascular risk factor
depends on additional studies on the genetic determinants of both VWF levels and
cardiovascular outcomes. Further studies on VWF levels as a predictor of the risk of
stroke (rather than CHD) in elderly or other high-risk population are also promising. Such
studies could lead to the clinical use of plasma VWF levels to refine the estimation of the
cardiovascular risk and of the expected benefit of antithrombotic agents.

Clinical Cardiology Spring 2004, Volume 9 Issue 1: 31-34

Measurement of von Willebrand factor as the marker of endothelial dysfunction in
vascular diseases
B Horvath, D Hegedus, L Szapary, et al

BACKGROUND: von Willebrand factor is a blood glycoprotein that is required for

normal hemostasis. Its level can be increased by endothelial cell damage.
HYPOTHESIS: von Willebrand factor is a suitable marker of endothelial dysfunction.
METHODS: von Willebrand factor activity was determined by ELISA in patients with
acute coronary syndromes, acute stroke and chronic vascular diseases, and was compared
with the values of healthy controls.
RESULTS: von Willebrand factor activity of patients in each group was significantly
higher (P<0.001) than that of the control group. The values of patients with acute
coronary syndrome and acute stroke were significantly higher (P<0.05 and P<0.01,
respectively) than those of patients with chronic vascular diseases. von Willebrand factor
activity was significantly higher in patients with acute coronary syndrome and acute
stroke (P<0.05 and P<0.01, respectively) on the sixth day than on admission.
CONCLUSIONS: By measuring von Willebrand factor activity, a considerable,
significant difference could be found between healthy people and chronic and acute
vascular patients. The routine measurement of von Willebrand factor activity in vascular
patients as an index of endothelial dysfunction may have clinical importance, because
detection of this marker can be a noninvasive way of assisting diagnosis and indicating
disease progression.

Orv Hetil. 2003 Dec 14;144(50):2471-6. Links

[Investigation of von Willebrand-factor as a marker of

endothelial dysfunction in atherosclerotic patients]
[Article in Hungarian]

Horváth B, Hegedüs D, Szapáry L, Márton Z, Alexy T, Koltai K, Gyevnár Z,

Juricskay I, Tóth K, Késmárky G.

Pécsi Tudományegyetem, Altalános Orvostudományi Kar, I. Belgyógyászati

Klinika.

OBJECTIVE: To determine von Willebrand-factor activity as the marker of

endothelium dysfunction in vascular diseases and to compare it to healthy
controls. METHODS: von Willebrand-factor activity was determined by enzyme-
linked immunosorbant assay (ELISA) in patients with acute coronary syndromes
(29 patients, 67 +/- 13 years), acute stroke (15 pts, 67 +/- 12 years) on admission,
2nd and 6th day; and chronic vascular diseases (56 pts, 67 +/- 10 years) and was
compared to the values of healthy controls (23 persons, 36 +/- 12 years).
RESULTS: von Willebrand-factor activity was significantly (p < 0.001) higher in
all the measured vascular patients than in the control group. The values of acute
patients were significantly (p < 0.05-0.001) higher than those of patients with
chronic vascular diseases. In the hospital phase von Willebrand-factor activity in
acute patients increased continuously and on day 6 was significantly (p < 0.05-
0.01) higher than on admission. von Willebrand-factor activity was significantly
(p < 0.05) higher in troponin positive patients with acute coronary syndromes
compared to the troponin negative subjects. CONCLUSIONS: von Willebrand-
factor was found to be a suitable marker of endothelial dysfunction. The higher
von Willebrand-factor activity in patients with vascular diseases compared to the
control group can be caused by the endothelial dysfunction and extensive
atherosclerosis. The significantly higher von Willebrand-factor activity in acute
disorders suggests the more severe endothelium dysfunction and could be related
to the development of acute event through increased platelet adhesion and
aggregation.
Am J Hematol. 1997 May;55(1):15-23. Links

Von Willebrand factor and soluble E-selectin in

hyperlipidaemia: relationship to lipids and vascular
disease.
Blann AD, Davis A, Miller JP, McCollum CN.

University Department of Medicine, The City Hospital, Birmingham, United

Kingdom.

Our objective was to determine whether endothelial cell products von Willebrand
factor and soluble E-selectin are related to serum lipids, lipoprotein (a), and
vascular disease in patients with hyperlipidaemia. In order to achieve our aim,
blood samples were obtained for four experiments from 1) 160 patients (49 with
symptomatic vascular disease) with hypercholesterolaemia and an equal number
of age and sex matched controls; 2) 31 patients who were studied serially before
and after successful resolution of their hypercholesterolaemia; 3) 15 patients with
hypertriglyceridaemia; and 4) 20 controls, half of whom consumed a lipid-rich
breakfast. von Willebrand factor and soluble E-selectin were measured by enzyme
linked immunosorbent assay (ELISA) using commercial reagents. In experiment
(1) von Willebrand factor was increased in the patients with
hypercholesterolaemia (P=0.0077) and was higher still in patients with vascular
disease (P<0.0001). Soluble E-selectin was not influenced by
hypercholesterolaemia or vascular disease. The correlation of von Willebrand
factor with total and LDL cholesterol (both P<0.001) remained after both age and
blood pressure were controlled. Experiment (2) showed that serial studies in
patients over an average of 7 months a reduction in total cholesterol was
associated with a reduction in von Willebrand factor (r=0.51, P=0.002).
Experiment (3) demonstrated that von Willebrand factor was not increased in
patients with hypertriglyceridaemia (median 8.9 mmol/L), and in experiment (4) a
lipid-rich breakfast taken by fasted, healthy controls produced an increase in
serum triglycerides (P<0.01) but did not influence von Willebrand factor over an
8 hour period. We conclude that von Willebrand factor, but not soluble E-selectin,
is raised in hypercholesterolaemia and therefore may be a potential indicator of
endothelial cell physiology in subjects with, or at risk of, atherosclerotic vascular
disease.
Central European Journal of Immunology 1/2004

abstract:

C-reactive protein correlates with markers of endothelial

dysfunction in type 1 diabetic patients

Centr Eur J Immunol 2004; 29 (1): 10-14

authors: Aleksandra Araszkiewicz, Magdalena Sobieska, Bogna

Wierusz-Wysocka,

The interaction between inflammatory and endothelial cells seem to play a crucial role in
the development of late vascular diabetic complications. The aim of our study was to
evaluate the level of CRP and some markers of endothelial function in type 1 diabetic
patients. Moreover, we assessed the relationship between CRP and those markers:
endothelin-1 (ET-1), metabolites of nitric oxide (NO2–), soluble form of Intercellular
Cell Adhesion Molecule-1 (sICAM-1), Vascular Cell Adhesion Molecule-1 (sVCAM-1),
sE-selectin, fibronectin and von Willebrand factor (vWF).
The study was performed in 98 type 1 diabetic patients (57 women and 41 men), aged
32.1±9.8 years, duration of disease 12.8±7.4 years and HbA1c 7.8±2.6%. Serum levels of
CRP, ET-1, sICAM-1, sVCAM-1, sE-selectin, fibronectin, metabolite of NO and vWF
were estimated using ELISA commercial test.
CRP, ET-1, NO2–, sICAM-1, sVCAM-1, vWF, sE-selectin and fibronectin were
significantly higher in diabetic patients in comparison with healthy subjects (p<0.05).
CRP and NO2– were markedly higher in diabetic patients with microangiopathy (CRP:
4.91±0.28 vs 2.33±0.28 mg/l, p<0.05; NO2–: 85.49±1.71 vs 55.48±3.59 µmol/l, p<0.05).
Moreover, we noticed positive correlation between CRP and markers of endothelial
dysfunction, except the level of sVCAM-1 and sE-selectin (p<0.05).
The results of this study might suggest association between inflammatory process and
endothelial dysfunction in diabetes.