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.
Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77005, USA.
Andrew
A
Yee
Yumiko
Y
Sakurai
Suzanne G
SG
Eskin
Larry V
LV
McIntire
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