Genetic modifiers of atherosclerosis and macrophage phenotypes

动脉粥样硬化和巨噬细胞表型的遗传修饰

基本信息

  • 批准号:
    10306932
  • 负责人:
  • 金额:
    $ 63.26万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

Summary Heart disease is the number one killer of men and women in the United States. Although the incidence of cardiovascular disease deaths has declined, it still accounts for ~1 out of every 3 deaths. Coronary artery disease (CAD) due to atherosclerosis was responsible for most of these deaths. Despite increased knowledge about CAD risk factors and the availably of drugs to treat them, the CAD problem has not been solved. Large human genome wide association studies have identified many common genetic variants associated with CAD, but only a small fraction of the heritable risk has been discovered. This proposal aims to perform mouse genetic and genomic studies to identify atherosclerosis modifier genes and genetic modifiers of macrophage foam cell lipid droplet metabolism and inflammation, yielding insights into the mechanisms that regulate these pathways. The first aim of the proposed studies involves identifying the responsible genes and genetic variation that give rise to in vitro macrophage phenotypes using sophisticated genetic and gene editing approaches. The second aim of the proposed studies is to identify the mouse atherosclerosis modifier gene in a genetic locus identified on chromosome 2. This aim will use sophisticated gene editing as well as a newer mouse model of atherosclerosis induced by treatment with an antisense oligonucleotide targeting the low density lipoprotein receptor. These findings may lead to novel drug targets and therapies to prevent or treat CAD. The relevance of the proposed studies is that they address a significant health concern, coronary artery disease, and will yield insight into the mechanisms that modify atherosclerosis susceptibility. The discovery of novel pathways and proteins that regulate atherosclerosis and foam cell cholesterol metabolism and inflammation offers hope for new modes of risk assessment, prevention, and therapy.
总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Jonathan D Smith其他文献

Similar promotion of Aβ1-42 fibrillogenesis by native apolipoprotein E ε3 and ε4 isoforms
  • DOI:
    10.1186/1742-2094-1-15
  • 发表时间:
    2004-08-16
  • 期刊:
  • 影响因子:
    10.100
  • 作者:
    David Sweeney;Ralph Martins;Harry LeVine;Jonathan D Smith;Sam Gandy
  • 通讯作者:
    Sam Gandy

Jonathan D Smith的其他文献

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{{ truncateString('Jonathan D Smith', 18)}}的其他基金

Project 1 - Genes to Function: Causal Genes and their Roles in Cardiomyocyte and Atrial Physiology
项目 1 - 发挥功能的基因:因果基因及其在心肌细胞和心房生理学中的作用
  • 批准号:
    10646358
  • 财政年份:
    2022
  • 资助金额:
    $ 63.26万
  • 项目类别:
Project 1 - Genes to Function: Causal Genes and their Roles in Cardiomyocyte and Atrial Physiology
项目 1 - 发挥功能的基因:因果基因及其在心肌细胞和心房生理学中的作用
  • 批准号:
    10410648
  • 财政年份:
    2022
  • 资助金额:
    $ 63.26万
  • 项目类别:
Molecular Medicine Training Program at Cleveland Clinic/Case Western Reserve University
克利夫兰诊所/凯斯西储大学分子医学培训项目
  • 批准号:
    10426323
  • 财政年份:
    2021
  • 资助金额:
    $ 63.26万
  • 项目类别:
Molecular Medicine Training Program at Cleveland Clinic/Case Western Reserve University
克利夫兰诊所/凯斯西储大学分子医学培训项目
  • 批准号:
    10620326
  • 财政年份:
    2021
  • 资助金额:
    $ 63.26万
  • 项目类别:
Molecular Medicine Training Program at Cleveland Clinic/Case Western Reserve University
克利夫兰诊所/凯斯西储大学分子医学培训项目
  • 批准号:
    10268038
  • 财政年份:
    2021
  • 资助金额:
    $ 63.26万
  • 项目类别:
Genetic modifiers of atherosclerosis and macrophage phenotypes
动脉粥样硬化和巨噬细胞表型的遗传修饰
  • 批准号:
    10626053
  • 财政年份:
    2021
  • 资助金额:
    $ 63.26万
  • 项目类别:
Oxidant resistant apoA1 in reverse cholesterol transport, inflammation and atherosclerosis
抗氧化剂 apoA1 在逆转胆固醇转运、炎症和动脉粥样硬化中的作用
  • 批准号:
    9451333
  • 财政年份:
    2016
  • 资助金额:
    $ 63.26万
  • 项目类别:
Mechanism of ApoA1 Lipidation by ABCA1 in HDL biogenesis
HDL生物合成中ABCA1对ApoA1脂化的机制
  • 批准号:
    9102483
  • 财政年份:
    2016
  • 资助金额:
    $ 63.26万
  • 项目类别:
Oxidant resistant apoA1 in reverse cholesterol transport, inflammation and atherosclerosis
抗氧化剂 apoA1 在逆转胆固醇转运、炎症和动脉粥样硬化中的作用
  • 批准号:
    9173990
  • 财政年份:
    2016
  • 资助金额:
    $ 63.26万
  • 项目类别:
ApoA1 lipidation by ABCA1 in HDL biogenesis
HDL 生物合成中 ABCA1 对 ApoA1 脂化
  • 批准号:
    10206232
  • 财政年份:
    2016
  • 资助金额:
    $ 63.26万
  • 项目类别:

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