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Low molecular weight fucoidan attenuates experimental abdominal aortic aneurysm through interfering the leukocyte-endothelial cells interaction

机译:低分子量岩藻依聚糖通过干扰白细胞与内皮细胞的相互作用来减轻实验性腹主动脉瘤

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摘要

Low molecular weight fucoidan (LMWF) is a sulfated polysaccharide extracted from Saccharina Japonica that presents high affinity for P-selectin and abolish selectin-dependent recruitment of leukocytes. We hypothesized that dietary intake of LMWF, as a competitive binding agent of P-selectin, could limit the inflammatory infiltration and aneurysmal growth in an Angiotensin II-induced abdominal aortic aneurysm (AAA) mouse model. The Gene Expression Omnibus database was used for gene expressions and gene set enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that focal adhesion was involved in the development of AAA. However, dietary intake of LMWF could limit the enlargement of AAA, decreasing maximal aortic diameter and preserving elastin lamellae. Although LMWF did not decrease the circulatory monocytes count and lower the expression of P-selectin in endothelium, it reduced macrophages infiltration in media and adventitia. Furthermore, matrix metalloproteinase expression was markedly downregulated, accompanied with reduced expression of inflammatory mediators, including interleukin 1β, tumor necrosis factor-α and monocyte chemotactic protein-1. The present study revealed a novel target for the treatment of AAA and the anti-inflammatory effects of LMWF.
机译:低分子量岩藻依聚糖(LMWF)是一种从日本糖藻提取的硫酸化多糖,对P-选择蛋白具有高亲和力,并消除了白细胞依赖选择素的募集。我们假设膳食摄入LMWF作为P选择素的竞争结合剂,可以限制血管紧张素II诱导的腹主动脉瘤(AAA)小鼠模型中的炎症浸润和动脉瘤的生长。 Gene Expression Omnibus数据库用于基因表达和基因组富集分析。京都基因与基因组百科全书途径富集分析表明,粘着斑参与了AAA的发展。但是,LMWF的饮食摄入可能会限制AAA的扩大,降低最大主动脉直径并保留弹性蛋白层。尽管LMWF不会减少内皮细胞中循环单核细胞的数量并降低P-选择素的表达,但它减少了巨噬细胞在培养基和外膜中的浸润。此外,基质金属蛋白酶的表达明显下调,同时炎症介质的表达降低,包括白介素1β,肿瘤坏死因子-α和单核细胞趋化蛋白-1。本研究揭示了一种新的靶点,用于治疗AAA和LMWF的抗炎作用。

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