dl-3-n-butylphthalide suppresses PDGF-BB-stimulated vascular smooth muscle cells proliferation via induction of autophagy.

AIMS: Vascular smooth muscle cells (VSMCs) played an important role in vascular remodeling. dl-3-n-butylphthalide (NBP) was extracted as a pure component from seeds of Apium graveolens Linn (Chinese celery) for protecting neurons activity, but the role of NBP on VSMCs was not clearly clarified.

MAIN METHODS: Cell proliferation was measured by MTS and flow cytometry. Western blot analysis and transmission electron microscopy were performed to analyze the relative protein expression and autophagosome. Moreover, the autophagic inhibitor and β-catenin inhibitor were used to evaluate the effects of NBP on autophagy and the function of β-catenin on cell proliferation respectively.

KEY FINDINGS: NBP significantly suppressed platelet derived growth factor-BB (PDGF-BB)-stimulated VSMC proliferation, and the inhibitory effects of NBP on proliferation were caused by inducing autophagy. In addition, the inhibitory effects of NBP on proliferation were associated with the β-catenin signaling pathway. Moreover, β-catenin overexpression reversed the induction effect of NBP on autophagy and the β-catenin inhibitor JW74 enhanced these effects.

SIGNIFICANCE: Our findings demonstrated that NBP protected VSMC from PDGF-BB-stimulated proliferation by inducing autophagy through suppression of the β-catenin signaling pathway, confirming the induction of autophagy might be a therapeutic strategy for use in the proliferative cardiovascular diseases.