von Willebrand Factor: More Than a Regulator of Hemostasis and Thrombosis

Abstract

von Willebrand factor (vWF) was first identified as an adhesive glycoprotein involved in hemostasis by Zimmermann in 1971. Since then, vWF has been shown to play a vital role in platelet adhesion, platelet binding to collagen and factor VIII protection. Recent studies have implicated vWF as a regulator of angiogenesis, smooth muscle cell proliferation, tumor cell metastasis and crosstalk in the immune system. In this review, we will discuss the aspects of vWF structure that facilitate its biological effects and speculate on its newly discovered and hypothesized roles in the pathogenesis of several diseases.

Von Willebrand Factor: Multimeric Structure and Functional Activity in Patients With Atrial Fibrillation With and Without Oral Anticoagulation

“…VWF mediates adhesion and aggregation of platelets at sites of vascular injury. [1][2][3] The molecule shows binding sites for coagulation factor VIII and platelet glycoproteins Ib/IX and IIb/IIIa, with 2 sites for collagen and 2 more for heparin. 2,4 vWF has 2 well-established biological functions: mediating adhesion and aggregation of platelets and acting as a carrier for factor VIII, protecting it from degradation, cellular uptake, or binding to the surface of activated platelets and endothelial cells.…”

“…[1][2][3] The molecule shows binding sites for coagulation factor VIII and platelet glycoproteins Ib/IX and IIb/IIIa, with 2 sites for collagen and 2 more for heparin. 2,4 vWF has 2 well-established biological functions: mediating adhesion and aggregation of platelets and acting as a carrier for factor VIII, protecting it from degradation, cellular uptake, or binding to the surface of activated platelets and endothelial cells. 2,5 Recent studies have provided evidence indicating that vWF regulates not only hemostasis and thrombosis but also the processes of angiogenesis, smooth muscle cell proliferation, tumor cell metastasis, and immune cell regulation.…”

“…2,4 vWF has 2 well-established biological functions: mediating adhesion and aggregation of platelets and acting as a carrier for factor VIII, protecting it from degradation, cellular uptake, or binding to the surface of activated platelets and endothelial cells. 2,5 Recent studies have provided evidence indicating that vWF regulates not only hemostasis and thrombosis but also the processes of angiogenesis, smooth muscle cell proliferation, tumor cell metastasis, and immune cell regulation. 2,6 Atrial fibrillation (AF) is the most commonly sustained cardiac arrhythmia and is associated with a high risk of stroke and thromboembolism.…”

“…2,5 Recent studies have provided evidence indicating that vWF regulates not only hemostasis and thrombosis but also the processes of angiogenesis, smooth muscle cell proliferation, tumor cell metastasis, and immune cell regulation. 2,6 Atrial fibrillation (AF) is the most commonly sustained cardiac arrhythmia and is associated with a high risk of stroke and thromboembolism. 7,8 Elevated vWF concentrations are associated with cardiovascular disease, 9 increased risk of ischemic heart disease, and the occurrence of acute ischemic stroke 10 ; these high levels of vWF are associated with the risk of stroke, even in the general population.…”

“…14,15 ADAMTS13 targets the A2 domain of vWF and specifically cleaves the protein between Tyr1605-Met1606, reducing the ULvWF to smaller and less active forms. 2 The failure to cleave large multimers will promote thrombosis. 16 Mean plasma level of vWF is 100 UI/dL, but the distribution among general population is broad, with 95% of values between 50 and 200 UI/dL.…”