Abstract
BackgroundAtherosclerosis (AS), which characterized with the accumulation of lipids on the vessel wall, is the pathological basis of many cardiovascular diseases (CVD) and seriously threatens human health. Resveratrol (RES) has been reported to be benefit for AS treatment. This research aimed to observe the effects of RES on AS induced by high-fat diet (HFD) and LPS in ApoE−/− mice and investigate the underlying mechanism.MethodsApoE−/− mice were fed with HFD companied with LPS to induce AS and RES was administrated for 20 weeks. Splenic CD4+ T cells were cultured and treated with anti-CD3/CD28 together with LPS, and RES was added. Serum lipids and the atherosclerotic areas of aortas were detected. The activation of CD4+ T cells were investigated both in vivo and in vitro and the expression of DNA methyltransferases (Dnmt) in CD4+ T cells were measured.ResultsIn vivo, administration of RES prevented HFD and LPS induced dysfunction of serum lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol) and HDL-C (high density lipoprotein cholesterol), ameliorated the thickened coronary artery wall and decreased the areas of atherosclerotic lesion on aortas. Besides, RES decreased the number of CD4+ T cells in peripheral blood, decreased the expression of CD25 and CD44, but not affected the expression of L-selectin (CD62L). In vitro, RES decreased the expression of Ki67, CD25 and CD44 in CD4+ T cells. Moreover, RES increased the secretion of IL-2, IL-10 and TGF-β1, decreased IL-6. In addition, RES decreased both the mRNA and protein level of Dnmt1 and Dnmt3b in CD4+ T cells.ConclusionThese results indicated that RES ameliorated AS induced by HFD companied with LPS in ApoE−/− mice, inhibited the proliferation and activation of CD4+ T cells and regulated the expression of Dnmt1 and Dnmt3b.
Highlights
Atherosclerosis (AS) is a chronic inflammatory disease [1, 2]
Compared to mice of high-fat diet (HFD) + LPS group, 5 mg/kg (BW)/ day of RES decreased content of Total cholesterol (TC), TG and non-HDLC at 10th week, and decreased content of TC, TG, LDLC and non-High density lipoprotein cholesterol (HDL-C), increased content of HDL-C at 20th week, suggesting that the ability of RES on regulating lipids in atherosclerotic mice induced by HFD and LPS will increase with prolonged use
We investigated that RES can inhibit the expression of Dnmt1 and Dnmt3b in CD4+ T cells and clarified that the decreased expression of Dnmt1 and Dnmt3b related to the inhibited activation of CD4+ T cells, but whether RES inhibited the activation of CD4+ T cells through down-regulating Dnmt1 and Dnmt3b remains unclear
Summary
Atherosclerosis (AS) is a chronic inflammatory disease [1, 2]. AS induces the progression of cardiovascular diseases (CVD) such as coronary heart disease and cerebral infarction, seriously threatens human health [3]. Dyslipidemia is a risk factor for the progression of AS and keep the serum lipids in a normal range is an important way to prevent AS [4]. Chronic inflammation, which accelerates the accumulation of immune cells on vessel wall, is another risk factor of AS [5]. CD4+ T cells as an important component in adaptive immune responses, powerfully regulates the inflammatory process [8, 9]. Activated CD4+ T cells further activate the immune response, increase the secretion of pro-inflammatory cytokines like interleukin-6 (IL-6), and decrease IL-10 and transforming growth factor-β1 (TGF-β1) [12,13,14]. Atherosclerosis (AS), which characterized with the accumulation of lipids on the vessel wall, is the pathological basis of many cardiovascular diseases (CVD) and seriously threatens human health. The activation of CD4+ T cells were investigated both in vivo and in vitro and the expression of DNA methyltransferases (Dnmt) in CD4+ T cells were measured
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