Von Willebrand factor deficiency and atherosclerosis

Abstract Von Willebrand factor (VWF) is a large multimeric glycoprotein that plays a major role in haemostasis, illustrated by the bleeding tendency in von Willebrand disease (VWD), the most common hereditary bleeding disorder caused by VWF deficiency or dysfunction. Elevated VWF levels are strongly associated with an increased risk of ischemic cardiovascular events. Whether this relation is causal, or whether increased VWF levels reflect disturbances of endothelial function remains to be elucidated. One possibility is that VWF participates in the process of atherogenesis. The aim of the current review is to determine whether VWF deficiency provides protection against the development of atherosclerosis in humans and animals. Results from animal studies suggest that, at arterial branch point predilection sites, VWF deficiency or blockage has a protective effect against atherosclerosis. Based on the available evidence, this potential protective effect of VWF deficiency can most likely be tracked to the VWF–platelet interaction. Sites involved in this interaction could prove attractive targets in future treatment and prevention of cardiovascular disease, an option that is already being explored in humans. An unequivocal protective effect of VWD on atherosclerosis has not been demonstrated in humans. However the interpretation of these results is hampered by several methodological weaknesses. In conclusion, VWF is probably a significant player in the multifaceted interaction between the haemostatic system and the atherosclerotic process which deserves further study.