| Objectives:Present study was designed to evaluate the improvement effect of a-linolenic acid ester of plant sterol (ALA-PS) on atherosclerosis (AS) in apolipoprotein E knock out (ApoE KO) mice and investigate the underling molecular mechanisms.Methods:14wild type C57BL/6mice were assigned to the control group and given normal chow.42ApoE KO mice (6weeks of age, male,12-15g) were randomly divided into high-fat diet (HFD), flaxseed oil (FO) and flaxseed oil containing ALA-PS (FO+ALA-PS) groups. HFD group were given a high fat diet contained of21%fat and0.15%cholesterol for18weeks. This high fat diet was further supplemented with5%(w/w) flaxseed oil for FO group. A combination of3.3%(w/w) ALA-PS (provided2%PS) mixture with flaxseed oil which provided equivalent ALA to FO group was added to the high-fat diet and used for FO+ALA-PS group.Results:1. Compared with control, a significantly atherogenic action was induced in ApoE KO mice given HFD, while the lesions at the whole aorta, aortic sinus and aortic arch of mice in FO+ALA-PS group were obviously decreased (P<0.05). In addition, mice fed HFD were characterized by increased infiltration of macrophages and inflammatory Ly-6C (high) monocyte, as well as pronounced intimal vascular smooth muscle cells (VSMC) contents compared with control (P<0.05). ALA-PS was capable of mitigating the accumulation of macrophages and monocytes, and inhibiting proliferation and migration of VSMC.2. ALA-PS improved lipid disorder in serum and liver induced by HFD. In addition, the mRNA and protein expressions of hepatic genes involved in cholesterol intake (LDLr, SR-BI), cholesterol efflux (LXRα, ABCA1), and triglyceride catabolism (PPARa, CPTIA, ACOX1) were significantly increased by intervention of ALA-PS. Moreover, mRNA and protein expressions of3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and sterol regulatory element binding protein2(SREBP-2) were found to be statistically decreased in ALA-PS-treated animals, as compared to those in HFD fed animals (P<0.05). Furthermore, supplement with ALA-PS apparently reversed the increased mRNA and protein expressions of sterol regulatory element binding protein-1c (SREBP-1c) and acetyl CoA carboxylase (ACC) in liver (P<0.05).3. ALA-PS had a significantly decline effect on plasma IL-1β, IL-6, TNF-α, MCP-1, sVCAM-1and sICAM-1, which were initially increased by HFD but not diminished by flaxseed oil intervention (P<0.05). In molecular level, ALA-PS dramaticlly decreased mRNA and protein expressions of aortic IL-1β,IL-6, TNF-α, MCP-1, VCAM-1and ICAM-1elevated by HFD (P<0.05). In circulating monocytes, up-regulated IL-1β, IL-6, TNF-α and MCP-1in response to HFD were almost completely counteracted by the ALA-PS supplement (P<0.05).4. ALA-PS consumption apparently decreased the concentrations of MDA and elevated the levels of GSH in serum and liver. In addition, high level of ROS in aorta induced by HFD was significantly reduced after exposed to flaxseed oil, and this depression effect was further improved by adding ALA-PS (P<0.05). Moreover, in mice given ALA-PS supplemented diet, mRNA and protein expressions of aortic p22phox, p47phox, p67phox and gp91phox were apparently less than those of HFD-fed mice (P<0.05). Conclusions:Dietary supplementation of ALA-PS was synergistically in ameliorating AS. Such functions were associated with the modification effects on lipid metabolism, system inflammation and oxidative stress, as well as gene and protein expressions of relative molecules involved in. |
PDF Full Text Request