von Willebrand factor: a marker of endothelial dysfunction in vascular disorders?

Abstract

The vascular endothelium is involved in the production of many important substances which are involved in a cardiovascular pathophysiology. One such substance which is synthesised by, and stored in, endothelial cells is von Willebrand factor (vWf). When released, vWf appears to mediate platelet aggregation and adhesion. Numerous clinical and experimental reports suggest that high vWf levels reflect damage to the endothelium or endothelial dysfunction. The close association between vWf and the processes of thrombus formation (thrombogenesis) or atherogenesis also suggests that high vWf levels may be a useful indirect indicator of atherosclerosis and/or thrombosis. The availability of a useful marker of endothelial dysfunction may have potential clinical value. The measurement of such a marker can perhaps be a non-invasive way of assisting in clinical diagnosis or as an indicator of disease progression. High vWf levels have also been shown to have prognostic value in patients with ischaemic heart disease, peripheral vascular disease and inflammatory vascular disease. However, there is limited information that increased vWf is actually casual in the progression of vascular disease and that measures aimed at reducing vWf levels will be beneficial. In addition, interpretation of raised plasma vWf levels is complicated by the fact that vWf may be an acute phase reactant. Further research is indicated to explore the predictive value of this marker in population studies and, perhaps, therapeutic approaches in (and the value of) modifying vWf levels or function.

Von Willebrand Factor, Soluble P-Selectin, and Target Organ Damage in Hypertension

“…As well as confirming the presence of endothelial, platelet, and hemorheological abnormalities in hypertension, 4,5,19 the present study shows a relationship between TOD and the endothelial marker von Willebrand factor, but not soluble P-selectin and conventional hemorheological markers, in hypertensive patients. The exact mechanisms by which this occurs or, indeed, whether TOD promotes endothelial damage or vice versa is unclear.…”

“…21 Von Willebrand factor plays a vital role in mediating platelet adhesion to damaged arterial walls, particularly at the high shear rates found in stenosed arteries, 22 forming a bridge between exposed subendothelial structures and the glycoprotein IIb/IIIa receptor on platelets. 5 Elevated levels of von Willebrand factor are also related to the incidence of ischemic heart disease. For example, the Caerphilly Heart Study 23 found a significant association between von Willebrand factor levels and incident ischemic heart disease, whereas the Hoorn Study 24 found a 3-fold increased incidence of cardiovascular mortality in those in the highest tertile of von Willebrand factor after adjustment for confounders.…”

“…4 For example, von Willebrand factor is widely regarded as a marker of endothelial cell damage/dysfunction, and elevated plasma levels are related to adverse cardiovascular outcomes. 5 Platelets are important in the process of both atherosclerosis and thrombosis, 6 and soluble P-selectin is a plasma marker of platelet activation that has been related to adverse cardiovascular prognosis. 7,8 Blood rheology is also important, as abnormalities of flow constitute 1 component of Virchow's triad of thrombogenesis.…”

Evaluation of Plasma von Willebrand Factor as a Biomarker for Acute Arterial Damage in Rats

“…In cultures of human umbilical vein endothelium, the rapid release of vWF lacks specificity and can be readily induced by addition of thrombin, fibrin, histamine, activated complement complex C5b-9, oxygen radicals (29), and peptidoleukotrienes (7). The (14).…”

Haemorheological, endothelial and platelet function in subjects with hypertension: relationship to cardiovascular risk and influence of antihypertensive treatment

“…von Willebrand Factor (vWF) has emerged as an important and readily measured marker of endothelial damage or dysfunction, and may also contribute to plasma viscosity. 10,11 Higher levels of vWF have been demonstrated in patients with both hypertension, isolated systolic hypertension and systolic-diastolic hypertension, and furthermore levels may be reduced to normal by effective blood pressure reduction. In patients with other risk factors, however, vWF levels remained raised despite control of blood pressure.…”