In vitro and ex vivo regulation of vascular smooth muscle cell growth and phenotypic modulation by sulphated polysaccharides.
Heparin and pentosan polysulphate (PPS), a semi-synthetic sulphated polysaccharide, affected the phenotypic modulation of primary or subcultured rabbit smooth muscle cells (SMC) and at the same time inhibited their proliferation in culture. PPS was 5 fold more potent than heparin. Ex vivo, after subcutaneous administration of PPS or heparin (8 mg/kg/day for 13 days), SMC isolated from treated rabbits were growth-inhibited. At the same time, they reversed promptly to the contractile state as evidenced by immunofluorescent detection of intracellular myosin or electron microscopy. This ex vivo inhibitory effect was related to the dose and the duration of treatment, and was lost if 6 hours elapsed between the final dose and removal of the aorta. Such an effect was also observed after oral treatment with PPS (200 mg/kg/day for 7 days).
Herbert
J M
JM
Sanofi Recherche, Toulouse, France.
Nuti
D
D
Paul
R
R
Maffrand
J P
JP
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006493:Heparin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000032:analysis / Q000166:cytology* / Q000187:drug effects; D009218:Myosins / Q000032:analysis; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D010641:Phenotype; D011134:Polysaccharides / Q000494:pharmacology*; D011817:Rabbits
D011134:Polysaccharides; D010426:Pentosan Sulfuric Polyester; D006493:Heparin; D009218:Myosins