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Am. J. Respir. Cell Mol. Biol., Vol 17, No. 1, 07 1997, 78-83.

Inhibitory effect of heparin on serotonin-induced hyperplasia and hypertrophy of smooth muscle cells

SL Lee, WW Wang, PM Joseph, CA Hales and BL Fanburg
Department of Medicine, New England Medical Center/Tufts University School of Medicine, Boston, MA 02111, USA.

Serotonin (5-HT) produces both hyperplastic and hypertrophic effects on smooth muscle cell (SMC) in culture. Heparin is known to inhibit serum- induced hyperplasia of SMC but has not been previously tested on the stimulatory effect of 5-HT on SMC. Our present data show that at 24 h heparin inhibited by 50% the stimulation of 3H-thymidine incorporation into bovine pulmonary artery SMC and at 7 days totally reversed both cellular proliferation and enlargement of SMC produced by 1 microM 5- HT. Heparin failed to alter 5-HT uptake by SMC, but inhibited the stimulation of tyrosine phosphorylation of GTPase-activating protein, a proposed intermediate in the 5-HT stimulatory process. Thus heparin inhibits both hyperplastic and hypertrophic effects of 5-HT on SMC, perhaps through the inhibition of a phosphorylated intermediate protein.


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Copyright © 1997 American Thoracic Society.