Ginsenoside Rb1 Enhances Plaque Stability and Inhibits Adventitial Vasa Vasorum via the Modulation of miR-33 and PEDF.

Xiaoyan Yang,Mei Ni,Lei Zhang,Xiaoling Liu,Hao Wen,Rui Li,Mei Dong,Hongyan Dai,Jiayi Hu,Lei Wang,Xiaorong Luan,Minghao Liu,Zihao Zhang,Huixia Lu,Rong Guo,Xue Zhang,Huili Lin

doi:10.3389/fcvm.2021.654670

Abstract

Background: Atherosclerosis is closely associated with proliferation of the adventitial vasa vasorum, leading to the atherosclerotic plaque progression and vulnerability. In this report, we investigated the role of Ginsenoside Rb1 (Rb1) on atherosclerotic plaque stabilization and adventitial vasa vasorum (VV) along with the mechanisms involved.Methods and Results: Apolipoprotein E-deficient (ApoE−/−) mice were fed with a high-fat diet for 20 weeks, and then Ginsenoside Rb1 (50 mg/kg/d, intraperitoneal) was given for 4 weeks. Rb1 treatment significantly inhibited adventitial VV proliferation, alleviated inflammation, decreased plaque burden, and stabilized atherosclerotic plaques in apoE−/− mice. However, the beneficial effects of Rb1 on atherosclerotic lesion was attenuated by overexpression of miR-33. The analysis from atherosclerotic plaque revealed that Rb1 treatment could result in an induction of Pigment epithelium-derived factor (PEDF) expression and reduction of the miR-33 generation. Overexpression of miR-33 significantly reverted the Rb1-mediated elevation of PEDF and anti-angiogenic effect.Conclusions: Ginsenoside Rb1 attenuates plaque growth and enhances plaque stability partially through inhibiting adventitial vasa vasorum proliferation and inflammation in apoE−/− mice. The anti-angiogenic and anti-inflammation effects of Rb1 are exerted via the modulation of miR-33 and its target gene PEDF.

Highlights

Atherosclerosis (AS), a chronic and progressive disease characterized by structural and functional changes in the vascular wall, is becoming a major health burden worldwide [1]
We found that Rb1-treated group had less vasa vasorum, indicating that Rb1 could inhibit proliferation of VV in plaques of apoE−/− mice (Figures 3A,B)
These results demonstrated that miR-33 has profound negative impact on the Rb1-mediated enhancement of plaque stability, reduction of plaque burden, anti-inflammation and inhibition of VV in apoE−/− mice

Summary

Introduction

Atherosclerosis (AS), a chronic and progressive disease characterized by structural and functional changes in the vascular wall, is becoming a major health burden worldwide [1]. Proliferation of the Ginsenoside Rb1 Stablizes Atherosclerotic Plaque adventitial vasa vasorum is responsible for atherosclerotic lesion progression and vulnerability, which is closely associated with a high risk of plaque rupture [3, 4]. Ginsenoside Rb1 is a representative component of ginseng which exhibits anti-angiogenesis, anti-obesity, anti-oxidative stress, anti-fatigue properties [5, 7]. We have proved Rb1 can inhibit angiogenesis by modulating pigment epithelium-derived factor (PEDF) in HUVECs [7, 8], it remains unclear whether Rb1 has the ability to suppress vasa vasorum proliferation in atherosclerotic lesions and to stabilize AS plaque. Atherosclerosis is closely associated with proliferation of the adventitial vasa vasorum, leading to the atherosclerotic plaque progression and vulnerability. We investigated the role of Ginsenoside Rb1 (Rb1) on atherosclerotic plaque stabilization and adventitial vasa vasorum (VV) along with the mechanisms involved

Methods

Results

Conclusion