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Abstract
Background. The aim of this study was to determine the correlation between hemodynamic forces
and proliferation of smooth muscle cells (SMC).
Methods. Bovine arterial SMC were seeded in a fibronectin-coated polystyrene cylinder at 5
× 105 cells/tube and allowed to reach confluence and to adhere for 48 hours. The experimental
groups were subjected to a laminar flow of 150 ml/min (9 dyne/cm2), 100 ml/min (6 dyne/cm2), and 50 ml/min (3 dyne/cm2) for 24 hours. The control group was subjected to similar incubation conditions without
flow. The cells in the experiments remained attached and viable. All experiments were
performed in triplicate or more.
Results. Shear stress significantly reduced (p < 0.001) the 24-hour incorporation of tritiated
thymidine and cell proliferation. This effect was proportional to the level of shear
stress and was still evident 24 hours after flow cessation. Results of flow cytometry
confirmed a lower percentage of SMC in S phase with increasing shear stress. Synthesis
of cell-associated proteins was increased twofold (p < 0.01) in SMC subjected to laminar
flow. SMC subjected to shear stress released a higher quantity of mitogens, including
a platelet-derived growth factor (PDGF)-like substance as detected by immunologic
testing. Fifty percent volume per volume conditioned serum-free medium from SMC subjected
to shear stress increased threefold the tritiated thymidine uptake in PDGF receptor-bearing
Swiss 3T3 cells as compared with conditioned serum-free medium from control SMC not
subjected to shear stress and twelvefold as compared with standard control. The release
of mitogens was proportional to the level of shear stress and was still evident 24
hours after flow cessation. The mitogenic activity was partially reduced (30%, p <
0.01) by an excess of monospecific anti-PDGF antibody.
Conclusions. We conclude that (1) increasing shear stress inhibits SMC proliferation and stimulates
the synthesis of cell-associated proteins and the release of mitogens and (2) decreasing
shear stress facilitates proliferation of SMC. Thus, in situations of arterial flow
separation, the increased release of mitogens from SMC subjected to high shear stress
and the increased proliferation rate and susceptibility to mitogens of SMC subjected
to very low shear stress may generate a critical condition that predisposes to the
development of atherosclerosis with early plaque formation in regions of low-flow
shear stress.
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Article info
Publication history
Accepted:
March 17,
1992
Identification
Copyright
© 1993 Published by Elsevier Inc.
