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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-08-2560.
Submitted August 20, 2002
Accepted November 17, 2002
Shear Stress Inhibits the Adhesion Molecule Expressions in Vascular Endothelial Cells Induced by Co-Culture with Smooth Muscle Cells
Jeng J Chiu*, Li J Chen, Pei L Lee, Chih I Lee, Leu W Lo, Shunichi Usami, and Shu Chien
Division of Medical Engineering Research, National Health Research Institutes, Taipei, Taiwan
Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, California, USA
* Corresponding author; email: jjchiu{at}nhri.org.tw.
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. In the present study, the potential role of SMCs in regulating the shear stress-induced gene expression in ECs has been examined using our parallel-plate co-culture flow system, in which these two types of cells were separated by a porous membrane. In this co-culture system, SMCs tended to orient perpendicularly to the flow direction, whereas the ECs were elongated and aligned with the flow direction. Under static condition, co-culture with SMCs induced EC gene expressions of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin, while attenuated that of endothelial nitric oxide synthase (eNOS). Shear stress significantly inhibited the SMC-induced adhesion molecule gene expressions. 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 co-cultured with fibroblasts instead of SMCs. Our findings indicate that under static condition co-culture with SMCs induces ICAM-1, VCAM-1, and E-selectin gene expressions in ECs. These co-culture effects are inhibited by shear stress and require specific interaction between ECs and SMCs in close contact.
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