Abstract 11102: Ginsenoside Rb2 Alleviated Atherosclerosis Progression by Inhibiting M1 Macrophages Polarization Induced by Microrna-216a

Abstract

Background: It has been reported that microRNA-216a (miR-216a) advanced atherosclerosis progression by promoting macrophage polarization to M1 pro-inflammation phenotype. Ginsenoside Rb2 (Rb2) is the major pharmacologically active compound extracted from ginseng. Bioinformatics predicted that Rb2 had a high affinity with miR-216a. In the present study, we aimed to investigate the effect of Rb2 on macrophages in atherosclerosis progression induced by miR-216a. Methods: ApoE -/- mice with miR-216a adenovirus infection and Rb2 intraperitoneal injection were used to explore the effect of Rb2 on miR-216a-mediated atherosclerosis development in vivo. Oil red O, Hematoxylin-Eosin (HE) and Masson's trichrome staining were performed to assess the thoracic aortic plaque progression and stability. Immunohistochemical staining was used to detect the M1 macrophages in plaque. Furthermore, macrophages transfected with miR-216a and treatment with Rb2 were used to explore the mechanism of Rb2 on M1 polarization in vitro. Neutral red phagocytic experiment and cholesterol efflux assay were performed to assess the role of Rb2 in lipid accumulation of M1 macrophages. Results: The results in ApoE -/- mice showed that Rb2 alleviated miR-216a-mediated atherosclerosis lesion area by 33%, and promoted plaque stability with a lipid accumulation decrease by 55% and a collage content increase by 250%. We further observed that Rb2 inhibited M1 macrophages in plaque by 76%. Mechanistically, the data from macrophages revealed that Rb2 reserved miR-216a-mediated Smad3 and IκBα protein expression to inhibit NF-κB-responsive genes, including M1 maker monocyte chemotactic protein-1 (MCP1) and tumor necrosis factor alpha (TNFα), and Rb2 attenuated miR-216a-mediated lipid deposit in M1 macrophages by decreasing lipid uptake and promoting cholesterol efflux. Conclusion: Our results first time showed that Rb2 alleviated atherosclerosis progression and stability induced by miR-216a. By inhibiting M1 macrophage polarization through Smad3/IκBα, Rb2 decreases lipid accumulation and increases collage content increase in plaque. The Rb2 could serve as a potential small molecule drug for atherosclerosis associated M1 polarization.