Effects of heparin on growth factor induced mitogenic and proliferative responses of rat pulmonary artery smooth muscle cells

AIM: To investigate whether heparin inhibits growth factor-induced mitogenic and proliferative responses of the pulmonary arterial smooth muscle cells (PASMC). METHODS: Rat PASMC were cultured in medium 199 containing 10% fetal bovine serum (FBS). Mitogenesis was monitored from [methyl-3H] thymidine ([methyl-3H] TdR) uptake and cell proliferation was monitored by cell counting. RESULTS: FBS (1%), platelet-derived growth factor (PDGF, 50 micrograms.L-1), fibroblast growth factor (FGF, 50 micrograms.L-1) or interleukin 1 alpha (IL-1 alpha, 100 ng.L-1) alone induced both rat PASMC mitogenesis and proliferation. FBS (10%) and the combination of FBS (1%) with PDGF (50 micrograms.L-1), FGF (50 micrograms.L-1), or IL-1 alpha (100 ng.L-1) increased mitogenesis of rat PASMC. Heparin (100 mg.L-1) inhibited rat PASMC proliferation (28% +/- 6%) and thymidine incorporation (27% +/- 7%) induced by FBS (10%), and also significantly inhibited cell proliferation 25% +/- 6%, 27% +/- 7%, and 20% +/- 4%, and [methyl-3H] TdR incorporation 23% +/- 7%, 26% +/- 6%, 20% +/- 6% induced by FBS (1%) in combination with PDGF (50 micrograms.L-1), FGF (50 micrograms.L-1), or IL-1 alpha (100 ng.L-1) respectively. The PASMC viability was not affected by heparin. CONCLUSION: Proliferation and mitogenesis of rat PASMC induced by PDGF, FGF, and IL-1 alpha was augmented by simultaneous exposure to FBS. Heparin produced an inhibition on the proliferation and mitogenesis of rat PASMC caused by these growth factors.