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

Am J Respir Cell Mol Biol. 1997 Jul;17(1):78-83. doi: 10.1165/ajrcmb.17.1.2727.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Cattle
  • Cell Division / drug effects
  • Cells, Cultured
  • DNA / biosynthesis
  • Heparin / pharmacology*
  • Hyperplasia
  • Hypertrophy
  • Kinetics
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology
  • Serotonin / metabolism
  • Serotonin / toxicity*
  • Serotonin Antagonists*
  • Thymidine / metabolism


  • Serotonin Antagonists
  • Serotonin
  • Heparin
  • DNA
  • Thymidine