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

Abstract

<b>Background:</b> 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. <b>Methods and Results:</b> 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. <b>Conclusions:</b> 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.