Improvement of von Willebrand factor proteolysis after prostacyclin infusion in severe pulmonary arterial hypertension

Background-The presence of dysfunctional von Willebrand factor (vWF) in pulmonary arterial hypertension (PAH) was suggested to be related to increased proteolysis. Methods and Results-In 10 patients with severe PAH, we studied the proteolysis of plasma vWF (VWF levels, multimeric distribution, proteolytic pattern, and cleaving protease activity) and hemodynamic variables (mean pulmonary artery pressure, cardiac index, and total pulmonary vascular resistance) at baseline and 30 days after initiation of continuous prostacyclin infusion. At baseline, VWF levels were significantly increased, VWF proteolysis was excessive, and vWF-cleaving protease activity remained normal. These biological abnormalities were reversible and paralleled the improvement of hemodynamics under vasodilator treatment with prostacyclin. Conclusions-The excessive proteolysis of vWF in PAH is likely to be related to an increased susceptibility of VWF to proteases induced by high shear rates rather than to an enhanced release of enzymes.