ABSTRACT
The phenotypic switch of vascular smooth muscle cells (VSMCs) is a major initiating factor for atherosclerotic cardiovascular diseases. Plateletderived growth factorBB (PDGFBB) initiates a number of biological processes that contribute to VSMC proliferation and phenotypic switch. Crocin, a component of saffron, has been reported to inhibit atheromatous plaque formation. However, the effects of crocin on PDGFBBinduced VSMC proliferation and phenotypic switch remain unclear. The aim of the present study was to investigate the role of crocin on PDGFBBinduced VSMCs proliferation and phenotypic switch and its underlying mechanisms. Cell proliferation and markers of VSMCs phenotypic switch were measured using a Cell Counting Kit8 assay and western blot analysis, respectively. The signaling pathways involved in the effects of crocin on VSMCs were validated by western blot analysis with or without the use of specific pathway inhibitors. Crocin significantly inhibited PDGFBBinduced VSMCs proliferation compared with the PDGFBB only group (P<0.05). In addition, crocin significantly abrogated the PDGFBBinduced increase in contractile protein αsmooth muscle actin, calponin and decrease in synthetic proteins osteopontin (OPN) in a concentration dependent manner (P<0.05). In addition, crocin slowed PDGFBBinduced Janus kinase (JAK)signal transducer and activator of transcription 3 (STAT3) and extracellular signalregulated kinase (ERK)/Kruppellike factor 4 (KLF4) signaling activation in VSMCs. By applying the JAK inhibitor (AG490) and ERK1/2 inhibitor (U0126), the results suggested that the crocin inhibited PDGFBBinduced VSMCs phenotypic switch through the JAK/STAT3 and ERK/KLF4 signaling pathways. These results suggested that crocin may effectively prevent PDGFBBinduced VSMCs proliferation and phenotypic switch and may be a promising candidate for the therapy of atherosclerotic cardiovascular diseases.
