TY - GEN
T1 - Influence of Fluid Shear Stress on Matrix Metalloproteinase Production in Endothelial Cells
AU - Sakamoto, N.
AU - Ohashi, T.
AU - Sato, M.
PY - 2009/12/1
Y1 - 2009/12/1
N2 - Arterial bifurcations are known to be common sites for formation of cerebral aneurysms. It has been reported that shear stress of more than 7 Pa under physiological conditions exerts on near the flow divider of the bifurcations. It is thus speculated that such high shear stress may induce production of matrix metalloproteinases (MMPs) in endothelial cells (ECs), leading to the aneurysm formation. However, the detailed mechanism is still unknown. In this study, we evaluated the effect of magnitude of shear stress on expressions of MMP- 2 and -9, known to degrade elastic fibers and associate with the early stage of formation of aneurysms. ECs isolated from human umbilical veins were exposed to shear stress of 2 Pa or 7 Pa for 24 hours using a parallel-plate flow chamber. After flow-exposure experiments, ECs were cultured with serumfree medium for 12 hours. Then, MMP-2 and -9 activities in the conditioned medium was detected by gelatin zymography. While activated MMP-2 expression did not change between 2Pa and 7Pa, pro MMP-2 activity increased with increasing the magnitude of shear stress. The level of pro MMP-9 activity also increased according to the increase in shear stress, and was significantly higher at 7 Pa compared to the static. These results suggest that higher shear stress near the flow divider at bifurcation of cerebral arteries may enhance degradation of elastic fibers in vessel walls, possibly leading to formation of cerebral aneurysms.
AB - Arterial bifurcations are known to be common sites for formation of cerebral aneurysms. It has been reported that shear stress of more than 7 Pa under physiological conditions exerts on near the flow divider of the bifurcations. It is thus speculated that such high shear stress may induce production of matrix metalloproteinases (MMPs) in endothelial cells (ECs), leading to the aneurysm formation. However, the detailed mechanism is still unknown. In this study, we evaluated the effect of magnitude of shear stress on expressions of MMP- 2 and -9, known to degrade elastic fibers and associate with the early stage of formation of aneurysms. ECs isolated from human umbilical veins were exposed to shear stress of 2 Pa or 7 Pa for 24 hours using a parallel-plate flow chamber. After flow-exposure experiments, ECs were cultured with serumfree medium for 12 hours. Then, MMP-2 and -9 activities in the conditioned medium was detected by gelatin zymography. While activated MMP-2 expression did not change between 2Pa and 7Pa, pro MMP-2 activity increased with increasing the magnitude of shear stress. The level of pro MMP-9 activity also increased according to the increase in shear stress, and was significantly higher at 7 Pa compared to the static. These results suggest that higher shear stress near the flow divider at bifurcation of cerebral arteries may enhance degradation of elastic fibers in vessel walls, possibly leading to formation of cerebral aneurysms.
KW - Cerebral aneurysm
KW - Endothelial cells
KW - High shear stress
KW - Matrix metalloproteinases
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U2 - 10.1007/978-3-540-92841-6_567
DO - 10.1007/978-3-540-92841-6_567
M3 - Conference contribution
AN - SCOPUS:84891946453
SN - 9783540928409
T3 - IFMBE Proceedings
SP - 2262
EP - 2263
BT - 13th International Conference on Biomedical Engineering - ICBME 2008
T2 - 13th International Conference on Biomedical Engineering, ICBME 2008
Y2 - 3 December 2008 through 6 December 2008
ER -