Pterostilbene attenuates experimental atherosclerosis through restoring catalase-mediated redox balance in vascular smooth muscle cells.

Atherosclerosis, the major risk of cardiovascular events, is a chronic vascular inflammatory disease. Pterostilbene is a naturally occurring dimethylated analog of resveratrol and has recently been demonstrated beneficial against cardiovascular diseases. However, the underlying mechanisms of pterostilbene on atherosclerosis remains elusive. Experimental atherosclerosis was induced by high-fat diet (HFD) in Apolipoprotein E knockout (ApoE-/-) mice. Pterostilbene was administered intragastrically for 16 weeks. We found that pterostilbene significantly attenuated thoracic and abdominal atherosclerotic plaque size in HFD-fed ApoE-/-mice, accompanied by modulated lipid profiles and reduced production of pro-inflammatory cytokines (including IL-6, IFN-γ and TNF-α). In addition, pterostilbene restored vascular redox balance in thoracic and abdominal aorta, evidencing by enhanced catalase (CAT) expression and activities, and decreased malondyaldheide and H2O2 production. Notably, pterostilbene specifically induced CAT expression and activities in VSMC of thoracic and abdominal aorta. In vitro, pterostilbene markedly promoted the expression and activity of CAT and decreased ox-LDL-mediated VSMC proliferation and intracellular H2O2 production, which was abolished by CAT siRNA knockdown or inhibition. Pterostilbene induced CAT expression was associated with inhibition of Akt, PRAS40, and GSK-3β signaling activation and upregulation of PTEN. Our data clearly demonstrated that pterostilbene exerted anti-atherosclerotic effect by inducing CAT and modulating VSMC function.