5 years ago

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

Resveratrol suppresses lipoprotein-associated phospholipase A2 expression by reducing oxidative stress in macrophages and animal models
Hongsheng Ouyang, Ziying Shen, Daxin Pang, Jiahuan Chen, Xiaochun Tang, Shengnan Sun, Wenzhi Ren, He Wang, Mingjun Zhang, Jiali Qu, Biao Yu, Qiangbing Yang
Scope Resveratrol is a naturally occurring polyphenolic compound with known cardioprotective, anti-inflammatory, and antioxidant properties. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with the risk of cardiovascular disease. Here, we investigated the effects of resveratrol on Lp-PLA2 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-PLA2 expression and reduced inflammation; lipopolysaccharide (LPS, 1 μg/mL), tumor necrosis factor-α (TNF-α, 10 ng/mL) and reactive oxygen species (ROS) were employed to stimulate an increase in Lp-PLA2 expression and ROS levels, and the stimulation was inhibited by resveratrol (50 μM) 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-PLA2 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-PLA2 expression. Resveratrol downregulates Lp-PLA2 expression in macrophages. Reactive oxygen species (ROS) upregulates Lp-PLA2 expression in macrophages. Resveratrol downregulates Lp-PLA2 expression in macrophages via the SIRT1 pathway. Resveratrol downregulates Lp-PLA2 expression in macrophages via ROS inhibition. Resveratrol upregulates SOD2 expression and downregulates PAF-AH activity, inflammation in a mouse model of chronic inflammation.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mnfr.201601112

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