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

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 Rb 1 (Rb 1 ) 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 Rb 1 (50 mg/kg/d, intraperitoneal) was given for 4 weeks. Rb 1 treatment significantly inhibited adventitial VV proliferation, alleviated inflammation, decreased plaque burden, and stabilized atherosclerotic plaques in apoE −/− mice. However, the beneficial effects of Rb 1 on atherosclerotic lesion was attenuated by overexpression of miR-33. The analysis from atherosclerotic plaque revealed that Rb 1 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 Rb 1 -mediated elevation of PEDF and anti-angiogenic effect. Conclusions: Ginsenoside Rb 1 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 Rb 1 are exerted via the modulation of miR-33 and its target gene PEDF.