Resveratrol ameliorates atherosclerosis induced by high-fat diet and LPS in ApoE−/− mice and inhibits the activation of CD4+ T cells

Abstract

Background 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. 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. Methods ApoE−/− 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. Results In 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. Conclusion These 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.

Bacterial lipopolysaccharide is associated with stroke

“…Indeed, LPS is found in carotid atherosclerotic plaque and blood LPS levels are higher in patients with carotid plaques compared to those without plaques 9 . LPS induces dysfunction of serum lipids that then accumulate on the aortic walls to form atherosclerotic plaques in ApoE−/− mice 10 , which might provide some insight into why LPS levels are higher in LAA patients.…”

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

“…Interestingly, although RSV inhibits nuclear factor kappa B (NF-κB) in some studies [61,62], RSV instead activates NF-κB in other studies [63][64][65][66]. Moreover, although RSV exacerbates atherosclerosis [26], it is also shown to prevent atherosclerosis [67,68]. Consistently, RSV also exacerbated inflammation state and superoxide production and diminishing aortic distensibility in aged mice [69].…”

Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

“…Resveratrol has been shown to attenuate HFD-induced obesity in mice by normalizing the nearly flattened circadian expression of PER2, CLOCK, and BMAL1 [ 181 ]. In ApoE −/− mice, resveratrol can inhibit either TMAO-induced atherosclerosis or HFD- and lipopolysaccharides (LPS)-induced atherosclerosis [ 182 ].…”