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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of macrophage liver X receptors as inhibitors of atherosclerosis
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Identification of macrophage liver X receptors as inhibitors of atherosclerosis

机译:鉴定巨噬细胞肝X受体作为动脉粥样硬化的抑制剂

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Recent studies have identified the liver X receptors (LXRα and LXRβ) as important regulators of cholesterol metabolism and transport. LXRs control transcription of genes critical to a range of biological functions including regulation of high density lipopro-tein cholesterol metabolism, hepatic cholesterol catabolism, and intestinal sterol absorption. Although LXR activity has been proposed to be critical for physiologic lipid metabolism and transport, direct evidence linking LXR signaling pathways to the pathogen-esis of cardiovascular disease has yet to be established. In this study bone marrow transplantations were used to selectively eliminate macrophage LXR expression in the context of murine models of atherosclerosis. Our results demonstrate that LXRs are endogenous inhibitors of atherogenesis. Additionally, elimination of LXR activity in bone marrow-derived cells mimics many aspects of Tangier disease, a human high density lipoprotein deficiency, including aberrant regulation of cholesterol transporter expression, lipid accumulation in macrophages, splenomegaly, and increased atherosclerosis. These results identify LXRs as targets for intervention in cardiovascular disease.
机译:最近的研究已经确定肝X受体(LXRα和LXRβ)是胆固醇代谢和运输的重要调节剂。 LXR控制着对一系列生物学功能至关重要的基因的转录,这些功能包括调节高密度脂蛋白胆固醇代谢,肝胆固醇分解代谢和肠道固醇吸收。尽管已经提出LXR活性对于生理性脂质代谢和运输至关重要,但是尚未建立将LXR信号传导途径与心血管疾病的病原体-疾病联系起来的直接证据。在这项研究中,在小鼠动脉粥样硬化模型的背景下,骨髓移植被用于选择性消除巨噬细胞LXR表达。我们的结果表明,LXRs是动脉粥样硬化的内源性抑制剂。另外,消除骨髓来源的细胞中的LXR活性可模拟丹吉尔病的许多方面,丹吉尔病是人类高密度脂蛋白缺乏症,包括胆固醇转运蛋白表达的异常调节,巨噬细胞中脂质的积聚,脾肿大和动脉粥样硬化的增加。这些结果确定了LXRs为干预心血管疾病的靶标。

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