Heparin regulates smooth muscle S phase entry in the injured rat carotid artery

Journal Article · Sat Aug 01 04:00:00 EDT 1987 · Circ. Res.; (United States)

DOI:https://doi.org/10.1161/01.RES.61.2.296· OSTI ID:6075580

Majesky, M W; Schwartz, S M; Clowes, M M; Clowes, A W

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 (/sup 3/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.

• Research Organization: Univ. of Washington, Seattle
• OSTI ID: 6075580
• Journal Information: Circ. Res.; (United States), Journal Name: Circ. Res.; (United States) Vol. 61:2; ISSN CIRUA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL CELLS
ANIMALS
ANTICOAGULANTS
ARTERIES
AZINES
BIOLOGICAL FUNCTIONS
BLOOD VESSELS
BODY
CARBOHYDRATES
CARDIOVASCULAR SYSTEM
CAROTID ARTERIES
CELL PROLIFERATION
DNA REPLICATION
DRUGS
FUNCTIONS
HEMATOLOGIC AGENTS
HEPARIN
HETEROCYCLIC COMPOUNDS
INHIBITION
INJURIES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MUCOPOLYSACCHARIDES
MUSCLES
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
POLYSACCHARIDES
PYRIMIDINES
RATS
RIBOSIDES
RODENTS
SACCHARIDES
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES