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

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.