Von Willebrand factor (vWF), a multifunctional haemostatic glycoprotein derived from endothelial cells and megakaryocytes, mediates platelet adhesion to injured subendothelium and binds coagulation factor VIII in the circulation. Native vWF is a disulphide-bonded homopolymer; the monomeric subunits, of apparent relative molecular mass (Mr) 220,000 (220K) are derived from an intracellular precursor estimated at 260-275K. Multimer assembly is preceded by the formation of dimers, linked near their C-termini, which then assemble into filamentous polymers. The importance of the removal of the large vWF pro-polypeptide during multimer assembly, and whether this or other stages of the complex post-translational processing require components specific to endothelial cells or megakaryocytes, is unknown. Here we report an analysis of the complete sequence of pre-pro-vWF and expression of the molecule in heterologous cells. The vWF precursor is composed of several repeated subdomains. When expressed in COS and CHO cells, it is cleaved and assembled into biologically active high relative molecular mass disulphide bonded multimers. This suggests that the information for assembly of this complex molecule resides largely within its primary structure.

Amino Acid Sequence↗

PubMedDate not supplied

Platelet response to hypotonic stress after storage at 4 C or 22 C.

Explore the source record for details and available documents.

Blood Cell Count↗

PubMedDate not supplied

Interaction of platelets and fibrin with injured rabbit aortic neointima. Effect of prostaglandin I2 and heparin.

Following aortic balloon deendothelialization, rabbits develop a neointima composed of smooth muscle cells and extracellular connective tissue. Injury of this neointima with a balloon catheter results in the accumulation of platelet aggregates and fibrin on the vessel surface. We studied platelet attachment and secretion following injury of the neointima and also the effect of prostaglandin I2 (PGI2) and heparin on these events. Platelet factor 4 was detected within the neointima by indirect immunofluorescence 30 minutes after neointimal injury. By using 51Cr-labeled platelets, it was possible to quantitate total platelet attachment following neointimal injury. When animals were sacrificed 30 minutes after reinjury, there were 4.46 X 10(6) platelets/cm2 of aortic surface in animals injured 10 days after initial balloon deendothelialization, and 3.75 X 10(6) platelets/cm2 of aortic surface in animals injured 29 days after initial injury. In these two groups, infusion of 850 ng/kg/min PGI2, along with a single infusion of 2500 units of heparin, inhibited fibrin deposition and reduced platelet attachment by 71% and 76%, respectively. Although infusion of heparin alone prevented fibrin deposition, neither heparin nor PGI2 individually reduced platelet attachment as profoundly as did their combined use.

Aminophylline↗