Fluid shear stress increases the intra-cellular storage pool of tissue-type plasminogen activator in intact human conduit vessels

We investigated the effect of shear stress on the expression of tissue-type plasminogen activator (t-PA) in intact human conduit vessels. Human umbili cal veins were exposed to high or low shear stress (25 vs < 4 dyn/cm(2)) at identical intraluminal pressure (20 mmHg) for 1.5, 3, and 6 h in a new com puterized biomechanical perfusion system. High shear perfusion induced a ma rked, time-dependent increase in t-PA immunostaining in both the endotheliu m and the media, t-PA relative to GAPDH gene expression increased by 54 +/- 14% in high-compared to low-sheared vessels (p = 0.002). By contrast, t-PA release into the perfusion medium was similar in vessels perfused under hi gh or low shear stress conditions. The results show that shear stress indep endently of pressure is a potent fluid mechanical stimulus for upregulation of the intracellular storage pool of t-PA in the vascular wall of fresh hu man conduit vessels. The shear effect is associated with an increased t-PA gene expression.