代謝に依存した生活習慣病における血管障害

DOI Web Site Web Site 参考文献22件 オープンアクセス
  • 櫛山 暁史
    明治薬科大学薬物治療学研究室
  • 高橋 雅弘
    明治薬科大学薬物治療学研究室
  • 櫛山 櫻
    国立国際医療研究センター看護大学校看護学部人間科学分野生命科学
  • 菊池 貴子
    公益財団法人朝日生命成人病研究所糖尿病代謝科
  • 浅野 知一郎
    広島大学大学院医系科学研究科医化学講座

書誌事項

タイトル別名
  • Metabolism-dependent Vascular Pathophysiology in Adult Diseases
  • タイシャ ニ イソン シタ セイカツ シュウカンビョウ ニ オケル ケッカン ショウガイ

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説明

<p>In adult diseases, chronic inflammation-related angiopathy is the main pathological condition of organ disorders such as arteriosclerosis, chronic kidney disease, and non-alcoholic steatohepatitis (NASH). Macrophages play an important role in chronic inflammation. For example, macrophage foaming is important for atherosclerosis development. In our study using Apolipoprotein E knockout mice, hyperglycemia caused by the administration of nicotinamide-streptozotocin, which is a non-obese type 2 diabetes model, promoted arteriosclerosis, while the administration of sodium glucose co-transporter 2 inhibitor markedly reduced lesions. In further studies, arteriosclerosis was ameliorated in resistin like molecule β knockout mice, or by xanthine inhibitors. Xanthine oxidase (XO) inhibitors also improved kidney damage in a diabetic renal disorder model using KK/Ay mice and liver damage in a NASH model using high-fat, high-sucrose trans fatty acid loading. These studies suggested that atherosclerosis can be ameliorated independently of glucose and/or lipid lowering therapy, by interventions targeting macrophages. In a study using J774.1 cells, acetylated low density lipoprotein (LDL), which is a typical denatured LDL, is taken up by macrophages regardless of glucose concentrations, but very low density lipoprotein (VLDL) is taken up into cells in a glucose-dependent manner. The glucose concentration-dependent uptake of VLDL was suppressed by XO inhibitors. In addition, the overexpression of XO increased the VLDL uptake and the VLDLR expression was also increased. The glucose and nucleic acid metabolism, which are associated with its metabolism, are involved in the uptake of VLDL. In conclusion, it was strongly suggested that macrophages regulate inflammation and intracellular lipids depending on metabolism and that they may be involved in angiopathy in adult diseases.</p>

収録刊行物

  • 薬学雑誌

    薬学雑誌 142 (5), 465-471, 2022-05-01

    公益社団法人 日本薬学会

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