期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 67, 期 46, 页码 12752-12760出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.9b05373
关键词
pterostilbene; CAT; vascular smooth muscle cells; atherosclerosis; inflammation
资金
- National Natural Science Foundation of China [81973322, 81573420, 31672307]
- Anhui Province Natural Science Foundation [1908085MH263, 1608085MC64, 1408085MH146]
- State Key Laboratory of Tea Plant Biology and Utilization [SKLTOF20180115]
- Key Projects of Anhui Province University Outstanding Youth Talent Support Program [gxgnfx2019025, gxyqZD2016235]
- Provincial Natural Science Research Project of Anhui Colleges [KJ2014A202]
- National Training Program of Innovation and Entrepreneurship for Undergraduates [201714098142]
- Wuxi Social Development Funds for International Science & Technology Cooperation [WX0303B010518180007PB]
- 136 talent project of Hefei Normal University
Atherosclerosis, the major risk of cardiovascular events, is a chronic vascular inflammatory disease. Pterostilbene is a naturally occurring dimethylated analogue of resveratrol and has recently been demonstrated to be beneficial against cardiovascular diseases. However, the underlying mechanisms of pterostilbene on atherosclerosis remain elusive. Experimental atherosclerosis was induced by a 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 formation in HFD-fed ApoE(-/-)mice, accompanied by modulated lipid profiles and reduced production of proinflammatory cytokines (including IL-6, IFN-gamma, and TNF-alpha). In addition, pterostilbene restored vascular redox balance in thoracic and abdominal aorta, evidenced by enhanced catalase (CAT) expression and activities, and decreased malondialdehyde and H2O2 production. Notably, pterostilbene specifically induced CAT expression and activities in the vascular smooth muscle cells (VSMCs) of thoracic and abdominal aorta. In vitro, pterostilbene markedly promoted the expression and activity of CAT and decreased ox-low-density lipoprotein (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-3 beta signaling activation and upregulation of PTEN. Our data clearly demonstrated that pterostilbene exerted an antiatherosclerotic effect by inducing CAT and modulating the VSMC function.
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