Resveratrol suppresses lipoprotein-associated phospholipase A2 expression by reducing oxidative stress in macrophages and animal models

Scope: Resveratrol is a naturally occurring polyphenolic compound with known cardioprotective, anti-inflammatory, and antioxidant properties. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is associated with the risk of cardiovascular disease. Here, we investigated the effects of resveratrol on Lp-PLA(2) expression in vitro and in vivo and explored the underlying mechanisms. Methods and results: Human monocytic cells (THP-1) were induced to differentiate into macrophages for an in vitro experimental model. Resveratrol suppressed Lp-PLA(2) expression and reduced inflammation; lipopolysaccharide (LPS, 1 mu g/mL), tumor necrosis factor-alpha (TNF-alpha, 10 ng/mL) and reactive oxygen species (ROS) were employed to stimulate an increase in Lp-PLA(2) expression and ROS levels, and the stimulation was inhibited by resveratrol (50 mu M) and other antioxidants. The inhibition of resveratrol was inversed partially by sirtuin 1 (SIRT1) inhibitors (Nicotinamide, 1-10 mM) (p<0.05). Next, a chronic inflammation mouse model induced by a HFD (high fat diet) supplemented with resveratrol 100 mg/kg/day orally for 12 weeks, resulted in resveratrol-induced decreases in the Lp-PLA(2) levels in the plasma and liver and increases in the superoxide dismutase 2 (SOD2) expression in the liver (p<0.05). Conclusion: Based on our results, the protective effects of resveratrol on cardiovascular events may be related to its ability to suppress Lp-PLA(2) expression.