Dietary Blueberries Attenuate Atherosclerosis in Apolipoprotein E-Deficient Mice by Upregulating Antioxidant Enzyme Expression

ArticleinJournal of Nutrition 140(9):1628-32 · September 2010with14 Reads
DOI: 10.3945/jn.110.123927 · Source: PubMed
Abstract
Protective effects of blueberries (BB) against atherosclerosis and potential underlying mechanisms in reducing oxidative stress were examined in apoE-deficient (apoE(-/-)) mice. ApoE(-/-) mice were fed an AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried whole BB for 20 wk. The mean lesion area for apoE(-/-) mice fed BB was reduced by 39% (P < 0.001) in the aorta sinus and 58% (P < 0.001) in the descending aorta compared with CD-fed mice. These atheroprotective effects were independent of the serum lipid profile or total antioxidant capacity (as measured by oxygen radical absorbance capacity). The concentration of a biomarker of lipid peroxidation, F(2)-isoprostane, was lower in liver of BB-fed mice (P < 0.05). Genes analyzed by RT-PCR array showed that 4 major antioxidant enzymes in aorta [superoxide dismutase (SOD) 1, SOD2, glutathione reductase (GSR), and thioredoxin reductase 1] were upregulated in BB-fed mice. Enzyme activities of SOD and GSR were greater (P < 0.05) in liver and/or serum of BB-fed mice than those of CD-fed mice. In addition, serum paraoxonase 1 activity in serum of BB-fed mice was also greater than that of CD-fed mice (P < 0.05) at the end of the study. These results suggest a protective effectiveness of BB against atherosclerosis in this apoE(-/-) mouse model. The potential mechanisms may involve reduction in oxidative stress by both inhibition of lipid peroxidation and enhancement of antioxidant defense.
    • "Besides having less atherosclerotic lesions, mice fed LCMUFA also displayed a more stable plaque morphology characterized by less lipid deposition, decreased accumulation of macrophages and downregulation of marker genes for inflammation and macrophage. Other types of dietary treatments in atherosclerosis mouse models, such as blueberries and sphingolipids, have also been shown to reduce atherosclerosis in mice without significantly affecting serum lipoproteins, and it is well known that statins decrease atherosclerosis in mice without significantly changing plasma lipids [17, 18]. In order to gain insight into the possible anti-atherogenic mechanisms of LCMUFA supplementation, we examined hepatic gene expression changes by RNA-Seq and qPCR analysis of the mice on the three diets. "
    [Show abstract] [Hide abstract] ABSTRACT: Scope: Fish oil-derived long-chain monounsaturated fatty acids (LCMUFA) containing chain lengths longer than 18 were previously shown to improve cardiovascular disease risk factors in mice. However, it is not known if LCMUFA also exerts anti-atherogenic effects. The main objective of the present study was to investigate the effect of LCMUFA on the development of atherosclerosis in mouse models. Methods and results: LDLR-KO mice were fed Western diet supplemented with 2% (w/w) of either LCMUFA concentrate, olive oil, or not (control) for 12 wk. LCMUFA, but not olive oil, significantly suppressed the development of atherosclerotic lesions and several plasma inflammatory cytokine levels, although there were no major differences in plasma lipids between the three groups. At higher doses 5% (w/w) LCMUFA supplementation was observed to reduce pro-atherogenic plasma lipoproteins and to also reduce atherosclerosis in ApoE-KO mice fed a Western diet. RNA sequencing and subsequent qPCR analyses revealed that LCMUFA upregulated PPAR signaling pathways in liver. In cell culture studies, apoB-depleted plasma from LDLR-K mice fed LCMUFA showed greater cholesterol efflux from macrophage-like THP-1 cells and ABCA1-overexpressing BHK cells. Conclusions: Our research showed for the first time that LCMUFA consumption protects against diet-induced atherosclerosis, possibly by upregulating the PPAR signaling pathway. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jun 2016
    • "Clinical study with volunteers consuming blueberry beverages have demonstrated improved insulin sensitivity in insulin-resistant subjects [163]. Blueberries could also be used for decreasing blood pressure, decreasing of blood cholesterol and, therefore, lowering of cardiovascular risk and atherosclerosis prevention164165166. Del Bo′ et al. [167] referred to the effect of 300 g of blueberries intake on selected markers of oxidative stress and antioxidant protection (endogenous and oxidatively-induced DNA damage) and of vascular function (changes in peripheral arterial tone and plasma nitric oxide levels) in males. "
    [Show abstract] [Hide abstract] ABSTRACT: Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry), and Ericaceae (blueberry, cranberry), belong to the best dietary sources of bioactive compounds (BAC). They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins) and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits.
    Full-text · Article · Oct 2015
    • "The potential mechanisms may involve reduction in oxidative stress by both inhibition of lipid peroxidation as enhancement of antioxidant defense. Wu et al. (2010) reported that 20 weeks of dietary supplementation with 1% freeze-dried BB resulted in a significant decrease of aortic lesions. The authors suggest that the atheroprotective effect of BB may be related to its antioxidative effect. "
    [Show abstract] [Hide abstract] ABSTRACT: The effects of supplementation with blueberry (BE) extract (Vaccinium ashei Reade) for 14 consecutive days on biochemical, hematological, histopathological and oxidative parameters in hypercholesterolemic rats were investigated. After supplementation with lyophilized extract of BE, the levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides were decreased. Histopathological analysis showed significant decrease (p < 0.05) of aortic lesions in hypercholesterolemic rats. Oxidative parameters showed significant reductions (p < 0.05) in oxidative damage to lipids and proteins and an increase in activities of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. The BE extract showed an important cardioprotective effect by the improvements in the serum lipid profile, antioxidant system, particularly in reducing oxidative stress associated with hypercholesterolemia and anti-atherogenic effect in rats.
    Full-text · Article · Jul 2015
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