Pristimerin suppresses the phenotypic switch of vascular smooth muscle cells in atherosclerosis through inhibiting the activation of JAK2/STAT3 pathway.

AIM: The aim of our research was to investigate the potential effect of pristimerin (Pris) on atherosclerosis (AS), and clarify its underlying molecular mechanisms. METHODS: The effect of Pris on atherosclerotic lesions were assessed by using HE staining and Oil red O staining. Moreover, serum lipid profiles also detected using the commercial reagent kits. Inflammatory factors expression was determined employing qRT-PCR. The proteins associated with the phenotypic transformation of VSMCs and JAK2/STAT3 pathway-related proteins were assessed using western blot, immunohistochemistry and immunofluorescence. The proliferation and migration of VSMCs were determined utilizing EdU and Transwell assay. RESULTS: We found that Pris could suppress atherosclerotic lesions in mice. Moreover, Pris ameliorated lipid metabolism disorders and inflammation, and inhibited the phenotypic transformation of VSMCs in mice. In ox-LDL-treated VSMCs, Pris could also inhibit the phenotypic transformation and inflammatory responses. Subsequently, Pris was demonstrated to inhibit JAK2/STAT3 pathway in both HFD-caused AS mice and ox-LDL-treated VSMCs. The inhibition of Pris on the phenotypic transformation and inflammatory responses in VSMCs could be reversed by Colivelin TFA. CONCLUSION: Pris could alleviate the progression of AS by inhibiting the phenotypic transformation of VSMCs and inflammatory responses via suppressing the activation of JAK2/STAT3 pathway.