Endothelial Cell–Derived Von Willebrand Factor, But Not Platelet-Derived, Promotes Atherosclerosis in Apolipoprotein E–Deficient Mice

Abstract

EC-VWF, but not Plt-VWF, contributes to VWF-dependent atherosclerosis by promoting platelet adhesion and vascular inflammation. Plt-VWF even in the absence of a disintegrin and metalloprotease with thrombospondin type I repeats-13, both in platelet and plasma, was not sufficient to promote atherosclerosis.

Alternative trafficking of Weibel‐Palade body proteins in CRISPR/Cas9‐engineered von Willebrand factor–deficient blood outgrowth endothelial cells

“…This raises the question of whether dysregulated endothelial chemokine release as a result of VWF deficiency may also affect atherogenesis. Several studies in murine models have indeed shown that VWF‐deficient mice are protected from experimental atherosclerosis . However, firm evidence for a similar protective effect in patients with VWD has so far not been found (reviewed in).…”

“…Several studies in murine models have indeed shown that VWF-deficient mice are protected from experimental atherosclerosis. [59][60][61] However, firm evidence for a similar protective effect in patients with VWD has so far not been found (reviewed in 62 ). In vitro IL-6 and IL-8 constitutive secretion did not show large differences between CTRL and VWF −/− BOECs ( Figure 5), which is consistent with previous observations that the bulk of newly synthesized IL-6 and IL-8 does not enter WPBs but is released via the constitutive secretion pathway.…”

Activated αIIbβ3on platelets mediates flow-dependent NETosis via SLC44A2

“…Although it is often assumed that only activated platelets bind leukocytes, recent studies have revealed that platelets captured under flow by VWF released from activated endothelial cells can recruit leukocytes (Doddapattar et al, 2018;Zheng et al, 2015). If VWF-GPIbα-dependent signaling is capable of promoting leukocyte binding, this may be highly relevant to the non-hemostatic platelet functions (particularly when other agonists are not available/abundant), but may also provide major mechanistic insights into the early recruitment of leukocytes during the initiation of DVT.…”

Proteolysis of Von Willebrand Factor Influences Inflammatory Endothelial Activation and Vascular Compliance in Atherosclerosis

“…In vivo molecular imaging has recently been used to confirm histological findings that arterial platelet adhesion in atherosclerosis is mediated by increased endothelial-associated von Willebrand factor (vWF) and exposure of the vWF A1 binding domain for the glycoprotein-Ibα (GPIbα) subunit of the platelet GPIb-IX-V complex ( 10 , 11 , 12 ). Accumulation of self-associated vWF on the endothelium in atherosclerosis has been attributed in part to impaired cleavage by ADAMTS-13 ( 12 , 13 , 14 ).…”