课题基金 / 基金详情

Novel insights into the molecular and cellular mechanism regulating lipid metabolism and atherosclerosis

Novel insights into the molecular and cellular mechanism regulating lipid metabolism and atherosclerosis
对调节脂质代谢和动脉粥样硬化的分子和细胞机制的新见解
批准号:
10551905
负责人:
Carlos Fernandez Hernando
金额:
$85.01万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-02-01 至 2024-01-31

项目摘要

项目成果

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中文摘要
翻译
项目总结 胆固醇稳态控制的改变会导致病理过程,包括 动脉粥样硬化是西方社会最常见的死亡原因。流行病学研究表明 确定了导致动脉粥样硬化形成的许多环境和遗传因素。特别是,高水平 低密度脂蛋白胆固醇(LDL-C)和低水平高密度脂蛋白胆固醇(HDL-C) 与心血管疾病(CVD)风险增加有关。除了蛋白质编码基因,非 编码RNA,包括microRNAs(MiRNAs),最近被证明在基因调控中起着关键作用 表情。MiRNAs表达的改变与包括心血管疾病在内的许多疾病有关。 我们以前的工作证明了miRNAs在调节高密度脂蛋白胆固醇和低密度脂蛋白胆固醇中的重要性。在……里面 特别是,我们小组和其他人的工作确定miR-33a/b和miR-148a是细胞的关键调节因子 胆固醇的外流和吸收,高密度脂蛋白的生物生成和低密度脂蛋白的清除。虽然这些研究强调了 操纵miRNAs控制循环高密度脂蛋白胆固醇和低密度脂蛋白胆固醇的治疗潜力 MiRNAs在控制脂肪和葡萄糖代谢中的作用仍然知之甚少。 深入研究miR-33a/b和miR-148a调节血糖和血糖的分子机制。 脂代谢,我们最近开发了一些独特的小鼠模型,使我们能够定义 MiR-33和miR-148A在体内控制脂代谢和动脉粥样硬化中的作用vbl.使用 尖端技术,我们将确定miR-33a/b和miR-148a所通过的监管网络 调节体内外脂代谢,评价抗miR-1的潜在治疗价值 33A/b和AntimiR-148A治疗心脏代谢性疾病,包括动脉粥样硬化和 代谢综合征。此外,我们将继续努力识别和表征新的非编码 RNA,包括调节脂质代谢和其他过程的长非编码RNA(LncRNAs) 影响心脑血管疾病的发展。 在另一个不同的主题中,我们还将研究调节 动脉粥样硬化的形成。我们假设Cav-1/Caveolae的表达受Flow调节,并介导低密度脂蛋白 动脉粥样硬化区的渗透和滞留导致动脉粥样硬化的进展。使用唯一 动物模型和创新的电子显微镜技术我们的目标是描述这个过程是如何 受监管的。
英文摘要
PROJECT SUMMARY Alterations in the control of cholesterol homeostasis can lead to pathological processes, including atherosclerosis, the most common cause of mortality in Western societies. Epidemiological studies have identified many environmental and genetic factors that contribute to atherogenesis. In particular, high levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased cardiovascular disease (CVD) risk. In addition to protein coding genes, non- coding RNAs including microRNAs (miRNAs) have recently shown to play a key role in regulating gene expression. Alteration in miRNAs expression has been associated to numerous diseases including CVD. Our previous work has demonstrated the importance of miRNAs in regulating HDL-C and LDL-C. In particular, work from our group and others identified miR-33a/b and miR-148a as key regulators of cellular cholesterol efflux and uptake, HDL biogenesis and LDL clearance. While these studies highlight the therapeutic potential of manipulating miRNAs to control circulating HDL-C and LDL-C, the effect of both miRNAs in controlling lipid and glucose metabolism remains poorly understood. To investigate in depth the molecular mechanism by which miR-33a/b and miR-148a regulate glucose and lipid metabolism, we have recently developed a number of unique mouse models that will allow us to define the contribution of miR-33 and miR-148a in controlling lipid metabolism and atherogenesis in vivo. Using cutting-edge techniques, we will identify the regulatory network through which miR-33a/b and miR-148a regulate lipid metabolism both in vitro and in vivo, and assess the potential therapeutic value of anti-miR- 33a/b and antimiR-148a therapy for treating cardiometabolic diseases including atherosclerosis and metabolic syndrome. Additionally, we will continue our efforts to identify and characterize novel non-coding RNAs, including long non-coding RNAs (lncRNAs) that regulate lipid metabolism and other processes that influence the development of CVD. In another different topic, we will also study the molecular mechanisms that regulate the initial steps of atherogenesis. We hypothesize that Cav-1/caveolae expression is regulated by flow and mediates LDL infiltration and retention in atheroprone areas leading to the progression of atherosclerosis. Using unique animal models and innovative electron microscopy technics we aim to characterize how this process is regulated.
期刊论文(16)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1093/cvr/cvx038
发表时间: 2017-04
期刊: Cardiovascular research
影响因子: 10.8
作者: [Xinbo Zhang;C. Fernández-Hernando]
通讯作者: Xinbo Zhang;C. Fernández-Hernando
MicroRNAs and Circular RNAs in Lipoprotein Metabolism.
脂蛋白代谢中的microRNA和圆形RNA。
DOI: 10.1007/s11883-021-00934-3
发表时间: 2021-05-10
期刊: CURRENT ATHEROSCLEROSIS REPORTS
影响因子: 5.8
作者: [Fernandez-Tussy, Pablo, Ruz-Maldonado, Inmaculada, Fernandez-Hernando, Carlos]
通讯作者: Fernandez-Hernando, Carlos
DOI: 10.1097/mol.0000000000000701
发表时间: 2020-10
期刊: Current opinion in lipidology
影响因子: 4.4
作者: [Zhang X, Fernández-Hernando C]
通讯作者: Fernández-Hernando C
DOI: 10.1016/j.semcdb.2017.11.026
发表时间: 2018-09
期刊: Seminars in cell & developmental biology
影响因子: 7.3
作者: [Singh AK, Aryal B, Zhang X, Fan Y, Price NL, Suárez Y, Fernández-Hernando C]
通讯作者: Fernández-Hernando C
7
    Role of lipid droplets in insulin resistance
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      10171841
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      $45.09万
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      2020
    • 负责人:
      Carlos Fernandez Hernando
    • 依托单位:
    Role of lipid droplets in insulin resistance
    • 批准号:
      10428493
    • 项目类别:
    • 资助金额:
      $45.09万
    • 财政年份:
      2020
    • 负责人:
      Carlos Fernandez Hernando
    • 依托单位:
    Role of lipid droplets in insulin resistance
    • 批准号:
      10643896
    • 项目类别:
    • 资助金额:
      $45.09万
    • 财政年份:
      2020
    • 负责人:
      Carlos Fernandez Hernando
    • 依托单位:
    Novel insights into the molecular and cellular mechanism regulating lipid metabolism and atherosclerosis
    • 批准号:
      10331792
    • 项目类别:
    • 资助金额:
      $85.01万
    • 财政年份:
      2017
    • 负责人:
      Carlos Fernandez Hernando
    • 依托单位:
    国内基金
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      2021JJ40433
    • 项目类别:
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      --
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      2021
    • 负责人:
      孙磊
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    寄主诱导梢腐病菌AreA和CYP51基因沉默增强甘蔗抗病性机制解析
    • 批准号:
      32001603
    • 项目类别:
      青年科学基金项目
    • 资助金额:
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    • 批准年份:
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    AREA国际经济模型的移植.改进和应用
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      18870435
    • 项目类别:
      面上项目
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      2.0万元
    • 批准年份:
      1988
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      史树中
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