Unité de Nutrition Humaine UMR1019, INRA, Centre de Recherche de Clermont-Ferrand/Theix, Groupe "Micronutriments, Métabolisme et Santé (MiMeS)", 63122 Saint Genès Champanelle, France.
Nutr Metab Cardiovasc Dis. 2012 Jan;22(1):72-80. doi: 10.1016/j.numecd.2010.04.011. Epub 2010 Aug 3.
Intake of anthocyanin-rich foods has been associated with a reduced risk of cardiovascular diseases. We recently reported that a nutritional supplementation with a bilberry anthocyanin-rich extract (BE) attenuates atherosclerotic lesion development in apolipoprotein E-deficient (apoE⁻/⁻) mice. However, the mechanism(s) of their preventive action are not completely understood. Anthocyanins may alter mRNA levels of genes related to atherosclerosis in cultured macrophages and endothelial cells, but in vivo studies remain scarce. The aim of the present study was to explore the in vivo mechanisms of action of the same bilberry extract, administered by supplementation at a nutritional level, in the aorta of apo E⁻/⁻ mice using a global transcriptomic approach. This study focused on the early stage of atherosclerosis development for better assessment of BE action on initiation mechanisms of this pathology. After a two week period, plasma lipid and antioxidant capacity were evaluated and the global genomic analysis was carried out using pangenomic microarrays. BE supplementation significantly improved hypercholesterolemia whereas the plasmatic antioxidant status remained unchanged. Nutrigenomic analysis identified 1261 genes which expression was modulated by BE in the aorta. Bioinformatic analysis revealed that these genes are implicated in different cellular processes such as oxidative stress, inflammation, transendothelial migration and angiogenesis, processes associated with atherosclerosis development/protection. Some of the most significantly down-regulated genes included genes coding for AOX1, CYP2E1 or TXNIP implicated in the regulation of oxidative stress, JAM-A coding for adhesion molecules or VEGFR2 implicate in regulation of angiogenesis. Other genes were up-regulated, such as CRB3, CLDN14 or CDH4 potentially associated with increased cell-cell adhesion and decreased paracellular permeability. These results provide a global integrated view of the mechanisms involved in the preventive action of bilberry anthocyanin-rich extract against atherosclerosis.
摄入富含花色苷的食物与降低心血管疾病风险有关。我们最近报道，用富含越橘花色苷的蓝莓提取物（BE）进行营养补充可减轻载脂蛋白 E 缺陷（apoE⁻/⁻）小鼠的动脉粥样硬化病变发展。然而，其预防作用的机制尚不完全清楚。花色苷可能会改变培养的巨噬细胞和内皮细胞中与动脉粥样硬化相关的基因的 mRNA 水平，但体内研究仍然很少。本研究的目的是使用全基因组转录组学方法，在 apoE⁻/⁻小鼠的主动脉中探索相同的越橘提取物以营养补充形式给药的体内作用机制。这项研究侧重于动脉粥样硬化发展的早期阶段，以便更好地评估 BE 对该病理学起始机制的作用。经过两周的时间，评估了血浆脂质和抗氧化能力，并使用全基因组微阵列进行了全基因组分析。BE 补充显著改善了高胆固醇血症，而血浆抗氧化状态保持不变。营养基因组分析确定了 1261 个基因，这些基因的表达受 BE 在主动脉中的调节。生物信息学分析表明，这些基因涉及不同的细胞过程，如氧化应激、炎症、血管内皮细胞迁移和血管生成，这些过程与动脉粥样硬化的发展/保护有关。一些表达被 BE 显著下调的基因包括编码 AOX1、CYP2E1 或 TXNIP 的基因，这些基因参与氧化应激的调节，编码 JAM-A 的基因或参与血管生成调节的 VEGFR2。其他基因被上调，如 CRB3、CLDN14 或 CDH4，可能与增加细胞间粘附和降低细胞旁通透性有关。这些结果提供了花色苷对动脉粥样硬化的预防作用涉及的机制的全面综合观点。
