VASCULAR-MONOCYTE ADHESION MOLECULE IN ATHEROGENESIS
动脉粥样硬化中的血管单核细胞粘附分子
基本信息
- 批准号:2903586
- 负责人:
- 金额:$ 21.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-01-01 至 2002-12-31
- 项目状态:已结题
- 来源:
- 关键词:apolipoprotein E atherosclerosis cell cell interaction gene expression genetic regulation immunocytochemistry interleukin 1 laboratory mouse laboratory rabbit leukocyte adhesion molecules lipopolysaccharides low density lipoprotein molecular cloning monoclonal antibody monocyte nucleic acid sequence protein structure function recombinant proteins tumor necrosis factor alpha vascular endothelium
项目摘要
DESCRIPTION (Adapted from Investigator's Abstract): The objective of this
proposal is to study the molecular basis of monocyte recruitment in
atherogenesis, focusing on the molecular and cell biology of a novel
monocyte adhesion-associated endothelial molecule, 151-ELAM. Preliminary
studies reveal a major role for 151-ELAM in binding of monocytes or
monocytoid cell lines to LPS, IL-1 and TNF-alpha stimulated mouse
endothelial cells (EC), to minimally modified low density lipoprotein
stimulated rabbit aortic EC and to endothelium of intact aortic segments
from cholesterol fed rabbits in en face binding assays. We shall explore
the expression and regulation of 151-ELAM, define its importance in monocyte
binding in atherogenesis, elucidate its structure, and ask whether it
represents a target for therapeutic modulation of atherogenesis. 1) The
expression and function of 151-ELAM in mouse and rabbit models of
atherogenesis will be explored. Analysis of the patterns of expression and
regulation using conventional and en face whole aorta immunohistologic
approaches will be important in understanding its role in endothelial
dysfunction and monocyte recruitment. Functional characterization of the
molecule, in comparison with other known adhesion molecules, will be pursued
in an ex vivo assay of monocyte binding to intact aortic segments from
fat-fed rabbits. The effect of anti- 151-ELAM treatment on the development
and progression of fatty streaks in fat-fed rabbit and apoE-deficient mouse
models will be assessed to confirm its role in vivo and to evaluate its
potential as a therapeutic target. 2) The role 151-ELAM plays in the
multi-step process of monocyte-endothelial interaction will be assessed
using flow based assays. The interaction of circulating leukocytes with
endothelium at sites of extravasation involves several sequential steps:
attachment, rolling, Galpha-i protein-linked activation and
activation-dependent adhesion and arrest. The step or step(s) blocked by
anti-151-ELAM MAbs will be assessed, thus providing critical insights into
the molecular role of 151-ELAM in monocyte recruitment. 3) cDNAs encoding
151 -ELAM will be cloned and characterized by standard procedures. Sequence
homologies may provide insights into 151-ELAM structure and function.
Transfectants or recombinant protein will facilitate characterization of its
adhesive properties and specificities. The proposed studies will elucidate
the structure of this novel vascular receptor and its role in monocyte
recruitment in atherogenesis. They may lead to new approaches to the
regulation of the atherogenic process.
描述(改编自《调查者摘要》):本报告的目的
建议研究单核细胞募集的分子基础
动脉粥样硬化的发生,专注于一种新的分子和细胞生物学
单核细胞黏附相关内皮分子,151-ELAM。初步
研究表明151-ELAM在单核细胞或
单核细胞系对内毒素、IL-1和肿瘤坏死因子-α刺激的小鼠的作用
内皮细胞(EC),到最小修饰的低密度脂蛋白
刺激兔主动脉内皮细胞及对完整主动脉段内皮细胞的影响
在EN Face结合分析中来自喂饲胆固醇的兔子。我们将探索
151-ELAM的表达和调控决定了其在单核细胞中的重要性
结合在动脉粥样硬化形成中的作用,阐明其结构,并询问它是否
代表了动脉粥样硬化形成的治疗调节的靶点。1)
151-ELAM在小鼠和兔实验性心力衰竭模型中的表达及功能
我们将探索动脉粥样硬化的形成机制。对表达方式的分析与探讨
常规和全面主动脉免疫组织学调控
对于理解它在内皮细胞中的作用,方法将是重要的
功能障碍和单核细胞募集。功能特性的研究
分子,与其他已知的黏附分子相比,将被追寻
在体外单核细胞与完整的主动脉节段结合的实验中
喂肥的兔子。抗151-ELAM治疗对发育的影响
脂肪喂养兔和载脂蛋白E缺陷小鼠脂肪条纹的进展
将对模型进行评估,以确认其在体内的作用并评估其
作为治疗靶点的潜力。2)151-ELAM在
将评估单核细胞-内皮细胞相互作用的多步骤过程
使用基于流动的分析方法。循环中白细胞与细胞因子的相互作用
渗出部位的内皮细胞包括几个连续的步骤:
附着、滚动、Galpha-I蛋白连接的激活和
依赖激活的黏附和停滞。被挡住的一步或一步(S)
将对抗151-ELAM单抗进行评估,从而为
151-ELAM在单核细胞募集中的分子作用。3)cDNA编码
151-ELAM将被克隆,并通过标准程序进行鉴定。数列
同源性可能提供对151-ELAM结构和功能的洞察。
转化子或重组蛋白将有助于其特性的研究
胶粘剂的性能和特性。拟议的研究将澄清
这种新型血管受体的结构及其在单核细胞中的作用
在动脉粥样硬化形成中的招募。它们可能会带来新的方法来解决
动脉粥样硬化形成过程的调控。
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 }}
LESLIE M MC EVOY其他文献
LESLIE M MC EVOY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('LESLIE M MC EVOY', 18)}}的其他基金
VASCULAR-MONOCYTE ADHESION MOLECULE IN ATHEROGENESIS
动脉粥样硬化中的血管单核细胞粘附分子
- 批准号:
6343570 - 财政年份:1998
- 资助金额:
$ 21.01万 - 项目类别:
VASCULAR-MONOCYTE ADHESION MOLECULE IN ATHEROGENESIS
动脉粥样硬化中的血管单核细胞粘附分子
- 批准号:
2839066 - 财政年份:1998
- 资助金额:
$ 21.01万 - 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:
$ 21.01万 - 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:
$ 21.01万 - 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:
$ 21.01万 - 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:
$ 21.01万 - 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:
$ 21.01万 - 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:
$ 21.01万 - 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:
$ 21.01万 - 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:
$ 21.01万 - 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:
$ 21.01万 - 项目类别: