Differing polarity of the constitutive and regulated secretory pathways for von Willebrand factor in endothelial cells.

Abstract

Abstract. von Willebrand factor (vWf) is secreted from endothelial cells by one of two pathways-a constitutive pathway and a regulated pathway originating from the Weibel-Palade bodies. The, molecular form of vWf from each of these pathways differs, with the most biologically potent molecules being released from Weibel-Palade bodies (Loesberg, C

Expression of the von Willebrand Factor in Atrial Endocardium is Increased in Atrial Fibrillation Depending on the Extent of Structural Remodeling

“…As vWF synthesized in the endothelium is secreted into the subendothelium as well as into the lumen, it is most likely that variable immunoreactivity for vWF in the endocardium reflects its synthetic activity in the overlying endothelial cells. 14 In contrast, it has been reported that the plasma levels of vWF are elevated in patients with mitral stenosis 21 or chronic AF. 22 Goldsmith et al have shown that the plasma levels of vWF in such patients are correlated with the extent of endothelial cell damage in the endocardium.…”

Differential Kinetics of Cell Surface Loss of von Willebrand Factor and Its Propolypeptide after Secretion from Weibel-Palade Bodies in Living Human Endothelial Cells

“…These forms of soluble VWF do not readily adhere to the surface membrane of platelets or endothelial cells but can bind to exposed extracellular matrix components and promote platelet adhesion following vessel damage (26). VWF stored in WPBs consists of a highly multimeric form of VWF (27,28). Stimulation of cultured endothelial cells with thrombin or histamine results in WPB exocytosis and the appearance of complex patches of this form of VWF on the cell surface (15,27).…”

von Willebrand factor multimerization and the polarity of secretory pathways in endothelial cells

“…Previous studies have addressed the polarity of VWF secretion, with conflicting results, [10][11][12][13][14] partly because they were carried out before it was established that there were three pathways for secretion of VWF. 8 van Buul-Wortelboer and collegues 10 used human umbilical vein endothelial cells (HUVECs) grown on collagen lattices to show that unstimulated (ie, basal plus constitutive) VWF release occurs at a 1:3 ratio (apical:basolateral), although the VWF quantified as basolateral release also took into account all the VWF cumulatively bound to the collagen fibers (80%), and so is an overestimation of the true basolateral rate of unstimulated release.…”

“…When cells were stimulated with phorbol 12-myristate 13-acetate (PMA), most of the VWF was released to the apical side, with no detectable change in the amount released basolaterally. In the same, year Sporn and colleagues 11 showed, using HUVECs grown on gelatin-coated polycarbonate membranes (3.0 mm pore size), that the amount of unstimulated VWF release (measured by 2-h metabolic labeling and analyzed by sodium dodecylsulfate [SDS]-polyacrylamide gel electrophoresis) into apical or basolateral chambers was approximately equal and contained similar multimeric forms, including multimers of all sizes. When cells were stimulated with the calcium ionophore A23187, 90% of the additional VWF came out basolaterally, with only high multimeric VWF being released.…”