Inhibitory Effect of Heparin on Serotonin-induced Hyperplasia and Hypertrophy of Smooth Muscle Cells

• Published in: American journal of respiratory cell and molecular biology Vol. 17; no. 1; pp. 78 - 83
• Main Authors: Lee, Sheu-Ling, Wang, Wei-Wei, Joseph, Patricia M, Hales, Charles A, Fanburg, Barry L
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01.07.1997; American Thoracic Society
• Subjects: 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
• ISSN: 1044-1549; 1535-4989
• 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.