Novel Function of Native Low-Density Lipoprotein in Inflammation

天然低密度脂蛋白在炎症中的新功能

基本信息

  • 批准号:
    10491145
  • 负责人:
  • 金额:
    $ 54.59万
  • 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:
    2021-09-21 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

SUMMARY Lipid and cholesterol-rich Western diet is a major risk factor for many non-communicable diseases, including cardiovascular disease, obesity, diabetes, metabolic syndrome, and inflammatory bowel disease (IBD). A common lipid derivative associated with the pathogenesis of these inflammatory and metabolic diseases is low-density lipoprotein (LDL) which is scavenged by its receptor (LDLR) expressed in almost all tissue. Despite the known function of LDL in atherosclerosis, its role in other diseases is poorly understood. Inflammation is a common trigger for atherosclerosis and other non-communicable diseases. However, whether native LDL, which is the most abundant physiological form of LDL, is involved in the inflammatory response is unknown. The goal of this study is to define a role of native LDL in inflammatory response, so the association of LDL with many human diseases can be explained. This critically important objective was stemmed from our preliminary studies in which we observed that mice having high blood LDL are highly susceptible to experimental colitis. Interestingly, mice defective in LDLR (Ldlr-/-) were relatively protective against colitis. Reduced colitis susceptibility of Ldlr-/- mice was associated with suppressed inflammation and decreased activation of inflammatory signaling pathways such as NF- kB and MAPK, pointing to an uncharacterized function of LDL/LDLR in inflammation. Indeed, we observed that native LDL stimulates macrophages in vitro to produce inflammatory molecules. Given that no study yet documented a role of native LDL in innate immune signaling and inflammatory responses, our observation underscored a novel mechanism of pathogenesis of inflammatory disorders associated with high blood LDL. We, therefore, hypothesize that endocytosis of LDL through LDLR induces inflammatory responses in myeloid cells causing inflammation, and such an inflammatory pathway imparts a major contribution in inflammatory disorders like colitis. This hypothesis will be tested through two specific aims: Aim 1. To dissect the pathway involved in LDL-mediated induction of inflammatory responses; Aim 2. To define the role of native LDL and its receptor in intestinal inflammation. Using biochemical and molecular biology techniques, we will explore signaling events and mechanisms involved in LDL/LDLR-mediated activation of NF-B and MAPK pathways. We will use Ldlr-/- mice and mouse models of colitis to investigate the in vivo relevance of LDL/LDLR in inflammatory disorders. Overall, this study will explore a novel biological function of native LDL which will help elucidate the pathogenic mechanism of diseases associated with high blood LDL. Furthermore, this study will decipher a yet unknown role of blood LDL in colitis pathogenesis. The findings of this study will open the opportunity to treat IBD and other non- communicable diseases by targeting LDL synthesis or LDLR downstream signaling pathways.
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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Hasan Zaki其他文献

Hasan Zaki的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Hasan Zaki', 18)}}的其他基金

The Inflammasome in the Regulation of Intestinal Glucose Homeostasis, Microbiota and Inflammation
炎症小体在肠道葡萄糖稳态、微生物群和炎症调节中的作用
  • 批准号:
    10368088
  • 财政年份:
    2021
  • 资助金额:
    $ 54.59万
  • 项目类别:
The Inflammasome in the Regulation of Intestinal Glucose Homeostasis, Microbiota and Inflammation
炎症小体在肠道葡萄糖稳态、微生物群和炎症调节中的作用
  • 批准号:
    10576289
  • 财政年份:
    2021
  • 资助金额:
    $ 54.59万
  • 项目类别:
The Inflammasome in the Regulation of Intestinal Glucose Homeostasis, Microbiota and Inflammation
炎症小体在肠道葡萄糖稳态、微生物群和炎症调节中的作用
  • 批准号:
    10209881
  • 财政年份:
    2021
  • 资助金额:
    $ 54.59万
  • 项目类别:
Novel Function of Native Low-Density Lipoprotein in Inflammation
天然低密度脂蛋白在炎症中的新功能
  • 批准号:
    10670376
  • 财政年份:
    2021
  • 资助金额:
    $ 54.59万
  • 项目类别:
Novel Function of Native Low-Density Lipoprotein in Inflammation
天然低密度脂蛋白在炎症中的新功能
  • 批准号:
    10363577
  • 财政年份:
    2021
  • 资助金额:
    $ 54.59万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 54.59万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了