title: Polyamine synthesis inhibition attenuates vascular smooth muscle cell migration.
abstract: Vascular smooth muscle cell migration, occurring after intimal injury, is a substantial clinical problem in atherosclerosis and restenosis after stenting. Here we investigate the effects of polyamine synthesis inhibition on vascular smooth muscle cell migration after maximal and submaximal growth stimulation with PDGF-AB or FCS. Vascular smooth muscle cells were obtained from mouse aorta explants. These cells coexpressed smooth muscle alpha-actin, PDGFRalpha and PDGFRbeta as demonstrated by immunocytochemistry. Treatment with a high (100 ng/ml) concentration of PDGF-AB stimulated DNA synthesis 6-fold and markedly elevated cell migration. PDGF-AB (100 ng/ml) increased cellular spermidine concentration 2-fold, but had no effect on spermine or putrescine levels. Treatment with the polyamine synthesis inhibitors CGP48664 (1 microM) and DFMO (5 mM) prevented the PDGF-AB-induced increase in spermidine and reduced spermine concentrations, but had no effect on PDGF-AB-stimulated DNA synthesis or cell migration. Cell migration after submaximal stimulation with either PDGF-AB (8 ng/ml) or FCS (8%) was, however, inhibited by the polyamine synthesis blockers. In summary, these data show that polyamine synthesis inhibition attenuates vascular smooth muscle cell migration under submaximal growth-stimulating conditions, suggesting that polyamines participate in regulation of cell migration and that treatment with polyamine synthesis inhibitors might reduce vascular smooth muscle cell migration after intimal injury.
authors.affiliation: Department of Physiological Sciences, Lund University, Lund, Sweden.
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.forename: Eva
authors.initials: E
authors.lastname: Ekblad
authors.forename: Per
authors.initials: P
authors.lastname: Hellstrand
authors.forename: Bengt-Olof
authors.initials: BO
authors.lastname: Nilsson
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005326:Fetal Proteins / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D001798:Blood Proteins; D005326:Fetal Proteins; D010982:Platelet-Derived Growth Factor; D011073:Polyamines; C095477:platelet-derived growth factor AB; D004247:DNA; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta