Abstract
The plasma glycoprotein von Willebrand factor (VWF) is exclusively synthesized in endothelial cells (ECs) and megakaryocytes, the precursor cells of platelets. Its primary function lies in hemostasis. However, VWF is much more than just a “fishing hook” for platelets and a transporter for coagulation factor VIII. VWF is a true multitasker when it comes to its many roles in cellular processes. In ECs, VWF coordinates the formation of Weibel–Palade bodies and guides several cargo proteins to these storage organelles, which control the release of hemostatic, inflammatory and angiogenic factors. Leukocytes employ VWF to assist their rolling on, adhesion to and passage through the endothelium. Vascular smooth muscle cell proliferation is supported by VWF, and it regulates angiogenesis. The life cycle of platelets is accompanied by VWF from their budding from megakaryocytes to adhesion, activation and aggregation until the end in apoptosis. Some tumor cells acquire the ability to produce VWF to promote metastasis and hide in a shell of VWF and platelets, and even the maturation of osteoclasts is regulated by VWF. This review summarizes the current knowledge on VWF’s versatile cellular functions and the resulting pathophysiological consequences of their dysregulation.
Highlights
Von Willebrand factor (VWF) is a multimeric glycoprotein found in the peripheral blood stream
We summarize the currently known functions of VWF in different cell types, thereunder endothelial cells (ECs), megakaryocytes, platelets, vascular smooth muscle cells and osteoclasts as well as cancer and immune cells
Some cancer cells are known to activate VWF expression to promote a more malignant phenotype. This activation was found to rely on epigenetic modifications of the VWF gene promotor, as investigated in tumor cell lines by Mojiri et al Several studies on the VWF-expressing osteosarcoma cell line Saos2 and glioma cell lines displayed a transcription factor binding pattern similar to the pattern found in active VWF promoters of ECs
Summary
Von Willebrand factor (VWF) is a multimeric glycoprotein found in the peripheral blood stream. Nakhaei-Nejad et al investigated HUVECs and EC-differentiated induced pluripotent stem cells and found that histone acetylase P300/CBP-associated factor (PCAF) is guided to the VWF promotor by binding of transcription activator GATA binding protein 6 (GATA6) [47]. Some cancer cells are known to activate VWF expression to promote a more malignant phenotype (see Chapter 2.8) This activation was found to rely on epigenetic modifications of the VWF gene promotor, as investigated in tumor cell lines by Mojiri et al Several studies on the VWF-expressing osteosarcoma cell line Saos and glioma cell lines displayed a transcription factor binding pattern similar to the pattern found in active VWF promoters of ECs. histone acetylation and DNA demethylation were observed in these VWF-expressing cell lines, indicating that epigenetic modifications can render the activation of VWF expression [49,50]
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