A validated system for simulating common carotid arterial flow in vitro: alteration of endothelial cell response.
Pulsations in blood flow alter gene and protein expressions in endothelial cells (EC). A computer-controlled system was developed to mimic the common carotid artery flow waveform and shear stress levels or to provide steady flow of the same mean shear stress in a parallel plate flow chamber. The pseudo-steady state shear stress was determined from real-time pressure gradient measurements and compared to the Navier-Stokes equation solution. Following 24 h of steady flow (SF: 13 dyne/cm2), pulsatile arterial flow (AF: average = 13 dyne/cm2, range = 7-25 dyne/cm2) or static conditions, heme oxygenase-1 (HO-1) and prostaglandin H synthase-2 (PGHS-2) mRNA and protein expressions from human umbilical vein endothelial cells were measured. Relative to steady flow, pulsatile arterial flow significantly attenuated mRNA upregulation of HO-1 (SF: 7.26 +/- 2.70-fold over static, AF: 4.84 +/- 0.37-fold over static; p < 0.01) and PGHS-2 (SF: 6.11+/-1.79-fold over static, AF: 3.54+/-0.79-fold over static; p < 0.001). Pulsatile arterial flow (4.57+/-0.81-fold over static, p < 0.01) also significantly reduced the steady-flow-induced HO-1 protein upregulation (7.99 +/- 1.29-fold over static). These findings reveal that EC can discriminate between different flow patterns of the same average magnitude and respond at the molecular level.
Yee
Andrew
A
Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77005, USA.
Sakurai
Yumiko
Y
Eskin
Suzanne G
SG
McIntire
Larry V
LV
D017536:Carotid Artery, Common / Q000502:physiology; D002478:Cells, Cultured; D003198:Computer Simulation; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008955:Models, Cardiovascular; D013314:Stress, Mechanical
D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2