Differential distribution of von Willebrand factor in endothelial cells. Comparison between normal pigs and pigs with von Willebrand disease.

Abstract

Endothelial cells were cultured from the thoracic aorta, inferior vena cava, and pulmonary artery of normal adult and young pigs as well as from pigs with von Willebrand disease (vWD). The von Willebrand factor (vWF) was estimated by ELISA in endothelial cell supernatants and lysates as well as by immunofluorescence of cells by use of either a polyclonal or a monoclonal antibody to vWF. In normal adult pigs, the content of vWF in supernatants and cell lysates was the highest in the pulmonary artery, lower in the inferior vena cava, and almost nil in the thoracic aorta. In the normal young pigs, vWF was higher in the inferior vena cava endothelial cell supernatants and lysates than in the pulmonary artery. Thus the synthesis of vWF by endothelial cells varies along the vascular tree and appears to be modulated by the age of the animals. In pigs with vWD, levels of vWF were slightly detectable in endothelial cells from the pulmonary artery (contrasting with levels of plasmatic vWF below 0.01 U/ml), but were undetectable in the thoracic aorta and inferior vena cava. Thus, if vWF plays a role in atherogenesis, this involves circulating, not its intracellular, form.

Cell type–specific regulation of von Willebrand factor expression by the E4BP4 transcriptional repressor

“…8 There is considerable variation in plasma VWF levels between individuals, 9 but as well, within an individual there is a marked regional heterogeneity in VWF expression in endothelial cells throughout the vasculature. [10][11][12] Significant efforts have been directed at understanding transcriptional regulatory mechanisms that control not only cell lineage-specific expression but also the observed variations in VWF levels. 11,13,14 Initial characterization of the 5Ј-flanking region of the VWF promoter identified the presence of positive and negative regulatory elements as far upstream as 2 kilobases (kb) from a single transcriptional start site.…”

Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras.

“…von Willebrand factor (vWF) is a large adhesive glycoprotein that is synthesized in the endothelial cells (1,2) and megakaryocytes (3,4) and present in platelet a granules (3,(5)(6)(7). Plasma vWF carries factor VIII (F.VIII) (8), prolongs its half-life (9-11), protects it from degradation by activated protein C (12,13), functions as a cofactor in thrombin-dependent cleavage of the F.VIII light chain (14), and modulates the activation of F.VIII and factor X (15,16).…”

A mouse model of severe von Willebrand disease: Defects in hemostasis and thrombosis

“…Animal models of type 3 vWd have been described in the dog and pig (4). Studies in the pig have been very useful to characterize vWf function, but, apart from the obvious problems related to the size and cost of the animals, this model was not ideal because homozygous pigs are not totally deficient in vWf (5). Furthermore, the pig colony is not syngeneic, making it difficult to study the importance of vWf in diseases involving many gene products such as atherosclerosis, in which its role is still controversial (6).…”