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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-08-2560.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2667-2674
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Shear stress inhibits adhesion molecule expression in
vascular endothelial cells induced by coculture with smooth muscle
cells
Jeng-Jiann Chiu,
Li-Jing Chen,
Pei-Ling Lee,
Chih-I Lee,
Leu-Wei Lo,
Shunichi Usami, and
Shu Chien
From the Division of Medical Engineering Research,
National Health Research Institutes, Taipei, Taiwan, Republic of China;
and the Department of Bioengineering and Whitaker Institute of
Biomedical Engineering, University of California-San Diego, La Jolla.
Vascular endothelial cells (ECs), which exist in close proximity to
vascular smooth muscle cells (SMCs), are constantly subjected to blood
flow-induced shear stress. Although the effect of shear stress on
endothelial biology has been extensively studied, the influence of SMCs
on endothelial response to shear stress remains largely unexplored. We
examined the potential role of SMCs in regulating the shear
stress-induced gene expression in ECs, using a parallel-plate
coculture flow system in which these 2 types of cells were separated by
a porous membrane. In this coculture system, SMCs tended to orient
perpendicularly to the flow direction, whereas the ECs were elongated
and aligned with the flow direction. Under static conditions, coculture
with SMCs induced EC gene expression of intercellular adhesion
molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and
E-selectin, while attenuating EC gene expression of endothelial
nitric oxide synthase (eNOS). Shear stress significantly inhibited
SMC-induced adhesion molecule gene expression. These EC responses under
static and shear conditions were not observed in the absence of close
communication between ECs and SMCs, and they were also not observed
when ECs were cocultured with fibroblasts instead of SMCs. Our findings
indicate that under static conditions, coculture with SMCs induces
ICAM-1, VCAM-1, and E-selectin gene expression in ECs. These coculture
effects are inhibited by shear stress and require specific interaction between ECs and SMCs in close contact.

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