Von Willebrand factor and angiogenesis: basic and applied issues

Abstract

To cite this article: Randi AM, Laffan MA. Von Willebrand factor and angiogenesis: basic and applied issues. J Thromb Haemost 2017; 15: 13-20.Summary. The recent discovery that von Willebrand factor (VWF) regulates blood vessel formation has opened a novel perspective on the function of this complex protein.VWF was discovered as a key component of hemostasis, capturing platelets at sites of endothelial damage and synthesized in megakaryocytes and endothelial cells (EC). In recent years, novel functions and binding partners have been identified for VWF. The finding that loss of VWF in EC results in enhanced, possibly dysfunctional, angiogenesis is consistent with the clinical observations that in some patients with von Willebrand disease (VWD), vascular malformations can cause severe gastrointestinal (GI) bleeding. In vitro and in vivo studies indicate that VWF can regulate angiogenesis through multiple pathways, both intracellular and extracellular, although their relative importance is still unclear. Investigation of these pathways has been greatly facilitated by the ability to isolate EC from progenitors circulating in the peripheral blood of normal controls and patients with VWD. In the next few years, these will yield further evidence on the molecular pathways controlled by VWF and shed light on this novel and fascinating area of vascular biology. In this article, we will review the evidence supporting a role for VWF in blood vessel formation, the link between VWF dysfunction and vascular malformations causing GI bleeding and how they may be causally related. Finally, we will discuss how these findings point to novel therapeutic approaches to bleeding refractory to VWF replacement therapy in VWD.

Perioperative von Willebrand factor dynamics are associated with liver regeneration and predict outcome after liver resection

“…Its primary functions are stabilization of factor VIII and cross‐linkage of platelets with the subendothelial matrix. Thus, vWF‐Ag is widely known as a key player in coagulation and primary hemostasis . However, vWF‐Ag also plays a role in platelet‐mediated liver regeneration.…”

Up-Regulated Expression of Matrix Metalloproteinases in Endothelial Cells Mediates Platelet Microvesicle-Induced Angiogenesis

“…Angiogenesis requires many coordinated activities, such as endothelial cell (EC) proliferation, migration, and alignment to form vessel-like tube [3]. Many regulators of angiogenesis both endogenous and pharmacological have been described and continue to be identified [4, 5]. …”

Effect of a high-fat diet and alcohol on cutaneous repair: A systematic review of murine experimental models

“…This weight range has been commonly observed in murine studies, mainly because the data are related to young and healthy animals [6,54]. Several articles did not provide the age of the animals, the number of animals per group, period of acclimatization, or light-dark cycle.…”

“…Skin repair can be organized into complementary phases such as hemostasis, inflammation, proliferation, and maturation [3–5]. Hemostasis presents as main feature interruption of hemorrhage through mechanisms such as vasoconstriction, formation of the platelet buffer and activation of blood coagulation [6,7]. The inflammatory phase consists of intense leucocyte recruitment to the wound area, removal of cellular and extracellular matrix debris, and synthesis of regulatory molecules such as cytokines and chemokine’s [8].…”