TY - JOUR
T1 - Effect of fluid shear stress on migration of vascular smooth muscle cells in cocultured model
AU - Sakamoto, Naoya
AU - Ohashi, Toshiro
AU - Sato, Masaaki
N1 - Funding Information:
This study was partly supported by Sasakawa Scientific Research Grants from the Japan Science Society, and by grants (No. 12480257 and No. 14208100) from the 21st Century COE Program “Future Medical Engineering Based on Bio-nanotechnology” granted to Tohoku University from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2006/3
Y1 - 2006/3
N2 - Migration of smooth muscle cells (SMCs) in hyperplasia is thought to have a correlation with blood flow conditions. In this study, the effect of shear stress applied to endothelial cells (ECs) on SMC migration was examined using a newly designed EC-SMC coculture model (CM), in which bovine SMCs and ECs were separated by a collagen layer and a membrane filter. After exposing the CM to shear stresses of 0.5, 1.0, or 1.5 Pa for 48 h, the number of SMCs migrating into the collagen layer was counted. Under static conditions, the migration of SMCs in the CM increased compared with SMCs cultured alone. Shear stress of 1.5 Pa significantly suppressed the SMC migration (p < 0.05) compared with the static CM. Media conditioned with the CM exposed to shear stress of 1.0 Pa (p < 0.05) and 1.5 Pa (p < 0.005) exhibited reduction in activated matrix metalloproteinase-2 (MMP-2) compared with the static CM, as analyzed by zymography. Addition of an inhibitor of nitric oxide (NO) synthase, N ω-nitro-L-arginine methyle ester, to the media inhibited the effect of 1.5 Pa shear stress on SMC migration but MMP-2 activity was unaffected. These results suggest that physiological shear stress has protective roles in atherosclerogenesis.
AB - Migration of smooth muscle cells (SMCs) in hyperplasia is thought to have a correlation with blood flow conditions. In this study, the effect of shear stress applied to endothelial cells (ECs) on SMC migration was examined using a newly designed EC-SMC coculture model (CM), in which bovine SMCs and ECs were separated by a collagen layer and a membrane filter. After exposing the CM to shear stresses of 0.5, 1.0, or 1.5 Pa for 48 h, the number of SMCs migrating into the collagen layer was counted. Under static conditions, the migration of SMCs in the CM increased compared with SMCs cultured alone. Shear stress of 1.5 Pa significantly suppressed the SMC migration (p < 0.05) compared with the static CM. Media conditioned with the CM exposed to shear stress of 1.0 Pa (p < 0.05) and 1.5 Pa (p < 0.005) exhibited reduction in activated matrix metalloproteinase-2 (MMP-2) compared with the static CM, as analyzed by zymography. Addition of an inhibitor of nitric oxide (NO) synthase, N ω-nitro-L-arginine methyle ester, to the media inhibited the effect of 1.5 Pa shear stress on SMC migration but MMP-2 activity was unaffected. These results suggest that physiological shear stress has protective roles in atherosclerogenesis.
KW - Coculture
KW - Endothelial cells
KW - Intimal hyperplasia
KW - Matrix metalloproteinase-2
KW - Nitric oxide
KW - Smooth muscle cell migration
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U2 - 10.1007/s10439-005-9043-y
DO - 10.1007/s10439-005-9043-y
M3 - Article
C2 - 16482415
AN - SCOPUS:33646428335
VL - 34
SP - 408
EP - 415
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
SN - 0090-6964
IS - 3
ER -