Endothelial Cell von Willebrand Factor Secretion in Health and Cardiovascular Disease

Abstract

The main function of von Willebrand factor (vWF) is to initiate platelet adhesion upon vascular injury. The hallmark of acute and chronical inflammation is the widespread activation of endothelial cells which provokes excessive vWF secretion from the endothelial cell storage pool. The level of vWF in blood not only reflects the state of endothelial activation early on in the pathogenesis, but also predicts disease outcome. Elevation in the blood level of vWF occurs either by pathologic increase in the rate of basal vWF secretion or by increased evoked vWF release from dysfunctional/activated endothelial cells (ECs). The increase in plasma vWF is predictive of prothrombotic complications and multi-organ system failure associated with reduced survival in the context of severe inflammatory response syndrome, type II diabetes mellitus, stroke and other inflammatory cardiovascular disease states. This chapter focuses on the role of high circulating vWF levels in thrombotic and inflammatory disease while paying attention to the emerging vWFrelated drug development strategies.

Embryonic periventricular endothelial cells demonstrate a unique pro-neurodevelopment and anti-inflammatory gene signature

“…Also, 31 of 46 genes associating with the “High shear stress-induced platelet activation” pathway were differentially expressed in PVEC vs. ABEC. There were significantly lower transcript levels of Von Willebrand factor ( Vwf , 1066-fold), integrin beta 3 ( Itgb3 , 14-fold), and selectin platelet ( Selp/ P-selectin, 3556-fold), all of which were consistent with an immature, yet less thrombogenic and less inflammatory PVEC phenotype 20 .…”

Venous and Arterial Endothelial Cells from Human Umbilical Cords: Potential Cell Sources for Cardiovascular Research

“…This indicated the formation of a functionally confluent endothelial monolayer, important for mediating anti-thrombogenic actions [ 31 ]. The von Willebrand factor (vWF) is a key player in hemostasis, stored in Weibel–Palade bodies in EC, and released both constitutively at low concentrations, and at events of inflammation in high amounts (reviewed in [ 32 , 33 ]). For example, EC activation by high concentrations of acrolein, a metabolite of the anti-cancer drug cyclophosphamide, induces a complete loss of vWF in HUVEC [ 34 ].…”

Angiotensin-converting enzyme 2, the complement system, the kallikrein-kinin system, type-2 diabetes, interleukin-6, and their interactions regarding the complex COVID-19 pathophysiological crossroads

“… 38 – 40 ARDS is characterized by an excessive inflammatory response, 41 – 43 damage to both alveolar epithelial 38 , 40 , 41 and vascular endothelial 39 , 44 , 45 cells, the subsequent breakdown of the alveolar-capillary barrier integrity, 38 , 42 , 46 impaired AFC, 40 , 41 , 45 excessive interstitial and parenchymal neutrophil migration, 38 , 43 , 45 and activation of alveolar macrophages, platelets, and pro-coagulant processes. 42 , 47 , 48 This may result in diffuse alveolar damage, 42 , 49 pulmonary fibrosis, 37 , 50 and impaired gas exchange, 42 , 51 leading to (refractory) hypoxemia 35 , 38 , 42 and possibly organ dysfunction. 40 , 47 , 52 …”

“… 70 Mechanical ventilation may promote ventilator-induced ALI, which is characterized by inflammation, increased vascular permeability, interstitial pulmonary edema, parenchymal infiltration, fibrosis, and thrombosis. 42 , 48 , 71 …”