Heparin Regulates Smooth Muscle S Phase Entry in the Injured Rat Carotid Artery

Smooth muscle cell (SMC) proliferation in injured arteries is inhibited by heparin, but the mechanism of inhibition is unknown. In particular, it is not clear whether heparin prevents exit of quiescent SMC from the resting state, inhibits progression through the prereplicative (G1) sequence, or acts...

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Bibliographic Details
Published in:Circulation research 1987-08, Vol.61 (2), p.296-300
Main Authors: Majesky, Mark W, Schwartz, Stephen M, Clowes, Monika M, Clowes, Alexander W
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cardiovascular system
Carotid Arteries - cytology
Carotid Arteries - drug effects
Carotid Arteries - enzymology
Carotid Arteries - pathology
Cell Division - drug effects
DNA - biosynthesis
Growth
Heparin - administration & dosage
Heparin - pharmacology
Infusions, Intravenous
Male
Medical sciences
Miscellaneous
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - enzymology
Ornithine Decarboxylase - metabolism
Pharmacology. Drug treatments
Rats
Rats, Inbred Strains
Thymidine - metabolism
Time Factors
Tritium
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Summary:Smooth muscle cell (SMC) proliferation in injured arteries is inhibited by heparin, but the mechanism of inhibition is unknown. In particular, it is not clear whether heparin prevents exit of quiescent SMC from the resting state, inhibits progression through the prereplicative (G1) sequence, or acts during DNA synthesis itself. In this study, induction of ornithine decarboxylase (ODC) activity was used as a marker of SMC entry into the cell cycle in an attempt to localize the site of heparin action during the initial hours after rat carotid injury. Rapid and transient induction of ODC activity was observed that reached a maximum (twenty-three-fold) 6 hours after wounding. Heparin failed to prevent ODC induction but greatly reduced frequencies of [H]thymidine-labelled SMC nuclei 33 hours after injury. Moreover, heparin infusion could be delayed for up to 18 hours after the injury event with no significant loss of antiproliferative effect. Further delays resulted in marked loss of growth inhibition. The results of these studies show that SMC rapidly and synchronously leave the resting state after injury and suggest that heparin acts late in the prereplicative (G1) sequence or early in S phase to inhibit SMC proliferation in damaged arteries.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.61.2.296