Role of Lipoprotein Receptors in Venous Thrombosis

脂蛋白受体在静脉血栓形成中的作用

基本信息

  • 批准号:
    8814273
  • 负责人:
  • 金额:
    $ 37.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-03-01 至 2016-02-29
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Deep venous thrombosis (DVT) is a significant clinical problem that can also lead to potentially fatal pulmonary embolism. Clinical studies reveal that thrombus resolution is central to the pathogenesis of post- thrombotic syndrome. Mechanisms that lead to thrombus resolution in DVT are not well understood at this time. It is clear, however, that optimal resolution of the thrombus requires an inflammatory response in which neutrophil and macrophages are recruited to the thrombus, and require proteases to degrade the matrix and thrombus. Our preliminary data employing mouse models of DVT reveal that genetic deletion of the LDLr results in enhanced thrombus resolution in mouse models of DVT. This appears to result from early recruitment of macrophages into the lesion in LDLr-deficient mice. This is accompanied by increased expression of MMP2; a protease implicated in thrombus resolution and decreased expression of PAI-1 in the thrombus isolated from LDLr-deficient mice. Further, we discovered that mice in which the LRP1 gene has been selectively deleted in macrophages also demonstrate enhanced thrombus resolution in a model of deep vein thrombosis. The central hypothesis of this application is that certain LDL receptor family members play important roles in modulating inflammatory events and protease activity thereby regulating clot resolution in mouse models of Deep Vein Thrombosis (DVT). The specific hypotheses to be tested are: 1) that the LDLr modulates thrombus resolution during DVT by modulating inflammation; 2) that LRP1 modulate thrombus resolution by regulating protease levels and by regulating signaling events in inflammation and 3) that we can engineer inhibitor molecules for receptor blockade that would enhance thrombus resolution in DVT. These hypotheses will be tested in the following specific aims: 1) Determine mechanisms by which the LDLr regulates thrombus resolution in mouse models of DVT; 2) Define the mechanisms by which LRP1 expressed in macrophages modulates thrombus resolution in mouse models of DVT and 3) Develop strategies for receptor blockade by designing antagonists for LDLR and LRP1 to enhance thrombus resolution in DVT.
描述(由申请人提供):深静脉血栓形成(DVT)是一个重要的临床问题,也可能导致潜在的致命性肺栓塞。临床研究表明,血栓消退是血栓后综合征发病机制的核心.导致DVT中血栓消退的机制目前还不清楚。然而,很明显,血栓的最佳消退需要炎症反应,其中中性粒细胞和巨噬细胞被募集到血栓中,并且需要蛋白酶来降解基质和血栓。我们采用DVT小鼠模型的初步数据显示,LDLr基因缺失导致DVT小鼠模型中血栓消退增强。这似乎是由于LDL r缺陷小鼠中巨噬细胞早期募集到病变中所致。这伴随着MMP 2表达的增加;在从LDL r缺陷小鼠分离的血栓中,MMP 2是一种与血栓消退有关的蛋白酶,派-1表达减少。此外,我们发现,在巨噬细胞中选择性删除LRP 1基因的小鼠在深静脉血栓形成模型中也表现出血栓消退增强。本申请的中心假设是某些LDL受体家族成员在调节炎症事件和蛋白酶活性中起重要作用,从而调节深静脉血栓形成(DVT)小鼠模型中的凝块消退。待检验的具体假设是:1)LDLr通过调节炎症来调节DVT期间的血栓消退; 2)LRP 1通过调节蛋白酶水平和调节炎症中的信号传导事件来调节血栓消退; 3)我们可以设计受体阻断抑制剂分子,以增强DVT中的血栓消退。将在以下特定目的中检验这些假设:1)确定LDLr调节DVT小鼠模型中血栓消退的机制; 2)确定巨噬细胞中表达的LRP 1调节DVT小鼠模型中血栓消退的机制; 3)通过设计LDLR和LRP 1拮抗剂来开发受体阻断策略,以增强DVT中的血栓消退。

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 }}

Dudley K. Strickland其他文献

Role for Low-Density Lipoprotein Receptor-Related Protein 1 in Vessel Wall Homeostasis
  • DOI:
    10.1016/j.jamcollsurg.2018.07.613
  • 发表时间:
    2018-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Brittany O. Aicher;Rebeca Galisteo;Selen C. Muratoglu;Areck A. Ucuzian;Dudley K. Strickland
  • 通讯作者:
    Dudley K. Strickland
NMR assignment of domain 3 of the receptor-associated protein (RAP)
  • DOI:
    10.1007/s10858-006-9036-7
  • 发表时间:
    2006-10-03
  • 期刊:
  • 影响因子:
    1.900
  • 作者:
    Donghan Lee;Joseph D. Walsh;Ping Yu;Molly Migliorini;Yibing Wu;Dudley K. Strickland;Yun-Xing Wang
  • 通讯作者:
    Yun-Xing Wang
NMR assignment of domain 2 of the receptor-associated protein
  • DOI:
    10.1007/s10858-006-9034-9
  • 发表时间:
    2006-07-25
  • 期刊:
  • 影响因子:
    1.900
  • 作者:
    Joseph D. Walsh;Donghan Lee;Ping Yu;Molly Migliorini;Dudley K. Strickland;Yun-Xing Wang
  • 通讯作者:
    Yun-Xing Wang
The low-density lipoprotein receptor-related protein-1 (LRP1) in Schwann cells controls mitochondria homeostasis in peripheral nerves
雪旺细胞中的低密度脂蛋白受体相关蛋白-1(LRP1)控制周围神经中的线粒体稳态
  • DOI:
    10.1016/j.pneurobio.2025.102796
  • 发表时间:
    2025-08-01
  • 期刊:
  • 影响因子:
    6.100
  • 作者:
    Stefano Martellucci;Melissa Heredia;Zixuan Wang;Thomas Whisenant;Dudley K. Strickland;Richard Sanchez;Takahito Arai;Morgan Zhang;Haoming Wang;Zhiting Gong;Kesava Asam;Brad E. Aouizerat;Gulcin Pekkurnaz;Yi Ye;Wendy M. Campana
  • 通讯作者:
    Wendy M. Campana
130 Characterization of a novel endothelial receptor, LR3, that defines a new class of receptors related to the LDL receptor family
  • DOI:
    10.1016/s0268-9499(97)80246-9
  • 发表时间:
    1997-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Todd A. Hembrough;Frances D. Battey;Jeffrey A. Winkles;Dudley K. Strickland
  • 通讯作者:
    Dudley K. Strickland

Dudley K. Strickland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('Dudley K. Strickland', 18)}}的其他基金

Upgrading the CVID Biosensor Core Facility with a Biacore 8K instrument
使用 Biacore 8K 仪器升级 CVID 生物传感器核心设施
  • 批准号:
    10176937
  • 财政年份:
    2021
  • 资助金额:
    $ 37.8万
  • 项目类别:
Role of LDL receptor family members in protecting the vasculature
LDL受体家族成员在保护脉管系统中的作用
  • 批准号:
    10321556
  • 财政年份:
    2017
  • 资助金额:
    $ 37.8万
  • 项目类别:
Role of LDL receptor family members in protecting the vasculature
LDL受体家族成员在保护脉管系统中的作用
  • 批准号:
    10078621
  • 财政年份:
    2017
  • 资助金额:
    $ 37.8万
  • 项目类别:
Role of LDL receptor family members in protecting the vasculature
LDL受体家族成员在保护脉管系统中的作用
  • 批准号:
    10532199
  • 财政年份:
    2017
  • 资助金额:
    $ 37.8万
  • 项目类别:
Mechanisms by which LRP1 Protects the Vasculature
LRP1 保护脉管系统的机制
  • 批准号:
    9002897
  • 财政年份:
    2014
  • 资助金额:
    $ 37.8万
  • 项目类别:
Mechanisms by which LRP1 Protects the Vasculature
LRP1 保护脉管系统的机制
  • 批准号:
    8722143
  • 财政年份:
    2014
  • 资助金额:
    $ 37.8万
  • 项目类别:
Role of Lipoprotein Receptors in Venous Thrombosis
脂蛋白受体在静脉血栓形成中的作用
  • 批准号:
    8435382
  • 财政年份:
    2012
  • 资助金额:
    $ 37.8万
  • 项目类别:
Role of Lipoprotein Receptors in Venous Thrombosis
脂蛋白受体在静脉血栓形成中的作用
  • 批准号:
    8320618
  • 财政年份:
    2012
  • 资助金额:
    $ 37.8万
  • 项目类别:
Role of Lipoprotein Receptors in Venous Thrombosis
脂蛋白受体在静脉血栓形成中的作用
  • 批准号:
    8623147
  • 财政年份:
    2012
  • 资助金额:
    $ 37.8万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    7264692
  • 财政年份:
    2007
  • 资助金额:
    $ 37.8万
  • 项目类别:

相似海外基金

Targeted ablation of cerebral atherosclerosis using supramolecular self-assembly
利用超分子自组装靶向消融脑动脉粥样硬化
  • 批准号:
    24K21101
  • 财政年份:
    2024
  • 资助金额:
    $ 37.8万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Body composition and atherosclerosis-related biomarkers in women with endometriosis
子宫内膜异位症女性的身体成分和动脉粥样硬化相关生物标志物
  • 批准号:
    23K15842
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Targeted multimodal stimuli-responsive nanogels for atherosclerosis imaging and therapy
用于动脉粥样硬化成像和治疗的靶向多模式刺激响应纳米凝胶
  • 批准号:
    2880683
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
    Studentship
The Epigenetic Regulator Prdm16 Controls Smooth Muscle Phenotypic Modulation and Atherosclerosis Risk
表观遗传调节因子 Prdm16 控制平滑肌表型调节和动脉粥样硬化风险
  • 批准号:
    10537602
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
Role of IL-6 trans signaling in atherosclerosis development and late-stage pathogenesis
IL-6反式信号传导在动脉粥样硬化发展和晚期发病机制中的作用
  • 批准号:
    10652788
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
Novel Mechanisms Underlying the Development of Atherosclerosis
动脉粥样硬化发展的新机制
  • 批准号:
    10589484
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
Alcohol Regulation of Endothelial Plasticity in Atherosclerosis
酒精对动脉粥样硬化内皮可塑性的调节
  • 批准号:
    10585070
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
From genotype to phenotype in a GWAS locus: the role of REST in atherosclerosis
GWAS 位点从基因型到表型:REST 在动脉粥样硬化中的作用
  • 批准号:
    10570469
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
2023 Atherosclerosis
2023 动脉粥样硬化
  • 批准号:
    10675221
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
The role of extracellular vesicle-associated MicroRNAs in HIV-associated atherosclerosis
细胞外囊泡相关 MicroRNA 在 HIV 相关动脉粥样硬化中的作用
  • 批准号:
    10619831
  • 财政年份:
    2023
  • 资助金额:
    $ 37.8万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了