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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.

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