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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Notch ligand Delta-like 4 blockade attenuates atherosclerosis and metabolic disorders
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Notch ligand Delta-like 4 blockade attenuates atherosclerosis and metabolic disorders

机译:Notch配体Delta-like 4阻滞减轻动脉粥样硬化和代谢紊乱

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摘要

Obese people have a greater risk of death from all causes, which is accounted for by atherosclerosis-induced cardiovascular disease. A disease complex called "cardiometabolic syndrome" is characterized by atherosclerosis, obesity, insulin resistance, and fatty liver. This disease has been linked to chronic inflammation, in which a key role is played by macrophages that are more abundant in atherosclerotic lesions than in healthy arteries. Fat tissue of obese individuals contains more macrophages than does the fat tissue of healthy-weight individuals. We know that in cultured macrophages a protein called Notch ligand delta-like 4 (D114) triggers various proinflammatory effects associated with atherosclerosis and metabolic disorders (1), and our goal in the present study was to replicate these findings in animals. Here, we report that suppression of D114 simultaneously attenuates several key components of cardiometabolic syndrome in a mouse model system.
机译:肥胖者因各种原因死亡的风险更高,这是由动脉粥样硬化引起的心血管疾病引起的。一种称为“心脏代谢综合征”的疾病复合体的特征是动脉粥样硬化,肥胖,胰岛素抵抗和脂肪肝。这种疾病与慢性炎症有关,在慢性炎症中,巨噬细胞在动脉粥样硬化病变中比在健康动脉中更为丰富,发挥着关键作用。肥胖个体的脂肪组织比健康体重个体的脂肪组织包含更多的巨噬细胞。我们知道,在培养的巨噬细胞中,一种称为Notch配体delta-like 4(D114)的蛋白质会引发与动脉粥样硬化和代谢紊乱相关的各种促炎作用(1),我们在本研究中的目标是在动物中复制这些发现。在这里,我们报告D114的抑制同时减弱了小鼠模型系统中心脏代谢综合征的几个关键组成部分。

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    Departments of Medicine Harvard Medical School, Boston, MA 02115;

    Departments of Medicine Harvard Medical School, Boston, MA 02115;

    Center for Systems Biology,Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Department of Research, Alnylam Pharmaceuticals, Cambridge, MA 02142;

    Department of Research, Alnylam Pharmaceuticals, Cambridge, MA 02142;

    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115;

    Center for Systems Biology,Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Departments of Medicine Harvard Medical School, Boston, MA 02115;

    Departments of Medicine Harvard Medical School, Boston, MA 02115;

    Center for Systems Biology,Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Departments of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115;

    Department of Immunology, Juntendo University School of Medicine, Tokyo 113, Japan;

    Departments of Medicine Harvard Medical School, Boston, MA 02115;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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