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.