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-H-3] thymidine ([methyl-H-3] TdR) uptake and cell proliferation was monitored by cell counting. RESULTS: FBS (1 %), platelet-derived growth factor (PDGF, 50 mu g . L-1), fibroblast growth factor (FGF, 50 mu g . 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 mu g . L-1), FGF (50 mu g . 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-H-3] TdR incorporation 23 % +/- 7 %; 26 % +/- 6 %, 20 % +/- 6 % induced by FBS (1%) in combination with PDGF (50 mu g . L-1), FGF (50 mu g . 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.