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Purpose: To investigate the inhibitory effect and mechanisms of heparin-derived oligosaccharide (HDO) on proliferation of vascular smooth muscle cells (VSMCs) induced by basic fibroblast growth factor(bFGF).Method:VSMCs proliferation was measured by MTT assays, cell cycle distribution was analyzed by flow cytometry.bEGF receptor1 and receptor2 (bFGFR1 and bFGFR2) mRNA expression levels were determined by RT-PCR, meanwhile bFGFR1 and bFGFR2 protein expression levels were detected by western blotting and immunocytochemical methods.Results: bFGF (5 ng·mL-1) significantly promoted VSMCs proliferation.HDO at concentrations of 0.01, 0.1 and 1 μmol·L-1 dose-dependently inhibited VSMCs proliferation, and the inhibition indices were 7.14%、 20.8% and 25.2% respectively.HDO inhibited cells in G1 phase entering into S phase at the same concentrations as above.Meanwhile, HDO at concentrations of 0.01, 0.1 or 1 μmol·L-1 inhibited bFGF-induced VSMCs bFGFR1 and bEGFR2 mRNA expression levels.In addition, bFGFR1 and bEGFR2 protein expression levels were significantly inhibited by 0.01, 0.1 or 1 μmol·L-1 HDO.Conclusion: HDO can inhibit VSMCs proliferation at a dose-dependent manner.The mechanism of HDO on proliferation of bFGF-induced VSMCs is associated with the inhibition of bFGFR1 and bFGFR2 expression levels.This altered molecular signature may explain one mechanism of HDO-mediated inhibition of VSMCs proliferation.