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 umbilical veins were exposed to high or low shear stress (25 vs < 4 dyn/cm2) at identical intraluminal pressure (20 mmHg) for 1.5, 3, and 6 h in a new computerized biomechanical perfusion system. High shear perfusion induced a marked, time-dependent increase in t-PA immunostaining in both the endothelium 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 high or low shear stress conditions. The results show that shear stress independently of pressure is a potent fluid mechanical stimulus for up-regulation of the intracellular storage pool of t-PA in the vascular wall of fresh human conduit vessels. The shear effect is associated with an increased t-PA gene expression.
Sjögren
L S
LS
Clinical Experimental Research Laboratory, Heart and Lung Insitute, Sahlgrenska University Hospital/Ostra, Göteborg University, Sweden.
Gan
L
L
Doroudi
R
R
Jern
C
C
Jungersten
L
L
Jern
S
S
D018076:DNA, Complementary / Q000096:biosynthesis / Q000502:physiology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006439:Hemodynamics; D006801:Humans; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000737:chemistry*; D010477:Perfusion / Q000295:instrumentation; D011312:Pressure; D012333:RNA, Messenger / Q000096:biosynthesis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D014664:Vasodilation
D018076:DNA, Complementary; D005343:Fibrinolytic Agents; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator