Key Points
- To determine how fluid shear stress influences the release of unusually large von Willebrand factor multimers from endothelial cells and identify factors in plasma that regulate their accumulation.
- Exposed cultured human umbilical vein endothelial cells (HUVECs) to steady venous-like or pulsatile arterial-like wall shear stress for 48–60 hours in serum-free or serum-containing media.
- Assayed the regulatory action of a 140,000–200,000 Da fraction from normal and severe von Willebrand's disease plasma cryosupernatant on luminal and subendothelial multimer release.
- HUVECs synthesized and released unusually large von Willebrand factor multimers under both venous-like and arterial-like shear conditions regardless of serum presence.
- A 140,000–200,000 Da activity in cryosupernatant specifically prevented the accumulation of these multimers in the overlying fluid without impairing their retrograde secretion into subendothelial collagen.
Structured PICO
PPopulationCultured human umbilical vein endothelial cells (HUVECs)
IInterventionExposure to cryosupernatant fraction of normal and severe von Willebrand's disease plasma
OOutcomeAccumulation of unusually large vWF multimers (ULvWFM) in the fluid above HUVEC monolayerssurrogate
A regulatory activity in plasma cryosupernatant prevents the accumulation of highly thrombogenic unusually large vWF multimers from endothelial cells, potentially inhibiting inappropriate platelet aggregation and thrombosis.