COBRE: OK MED RES FOUND: P5: ROLE OF PROTEOGLYCAN IN ATHEROGENESIS
COBRE:确定医学研究结果:P5:蛋白聚糖在动脉粥样硬化中的作用
基本信息
- 批准号:7610581
- 负责人:
- 金额:$ 25.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-01 至 2008-06-30
- 项目状态:已结题
- 来源:
- 关键词:AnabolismAnimal ModelApolipoprotein EApolipoproteins BArterial Fatty StreakAtherosclerosisBindingBlood VesselsCellsChondroitin SulfatesCollagenComputer Retrieval of Information on Scientific Projects DatabaseDevelopmentEndothelial CellsFundingGlycosaminoglycansGoalsGrantHistologicHumanImmunohistochemistryIn VitroInstitutionLesionLipoprotein BindingLipoproteinsLocalizedLow Density Lipoprotein ReceptorMagnetic Resonance ImagingMeasuresMediatingModificationMusPathogenesisPathologyProteinsProteoglycanResearchResearch PersonnelResourcesRoleSmooth Muscle MyocytesSourceStandards of Weights and MeasuresStructureTestingTransforming Growth Factor betaUnited States National Institutes of Healthatherogenesisbiglycandecorindermatan sulfate proteoglycanintravital microscopymouse modelversican
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
The goal of this proposal is to investigate the role of chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycan biosynthesis in atherogenesis. As an atherosclerotic lesion develops in the blood vessel wall, CS and DS proteoglycans biglycan, decorin, and versican accumulate. Because lipoproteins bind in vitro to
proteoglycans and co-localize with them in the atherosclerotic lesion, it has been hypothesized that increased proteoglycan biosynthesis by cells in the vessel wall is atherogenic. Biglycan is a likely candidate proteoglycan for binding and retaining lipoproteins since it binds atherogenic lipoproteins in vitro, colocalizes with apolipoprotein B (apoB) and E (apoE) in human atherosclerotic lesions, and more closely colocalizes with apoB and apoE in mouse lesions than decorin. Furthermore, because biglycan has both protein and glycosaminoglycan (GAG)-mediated interactions with other proteins (e.g. collagens, lipoproteins, TGFbeta), we hypothesize that these interactions are important to the structure and development of the lesion in the vascular wall. To test these hypotheses our three aims focus on measuring and characterizing atherosclerosis in 3 animal models, In specific aim 1, we will determine whether increased biosynthesis of biglycan by endothelial cells can exaggerate the development of atherosclerosis. In specific aim 2, we will determine whether increased biosynthesis of biglycan by vascular smooth muscle cells can exaggerate the development of atherosclerosis. In specific aim 3, we will determine whether the GAG modifications of biglycan are important for atherosclerotic lesion development and structure. All three mouse models will be made atherogenic by crossing them to either low-density lipoprotein receptor deficient or apolipoprotein E deficient mice. Our objectives with these mouse models of atherosclerosis are to determine the roles increased biosynthesis and GAG modification of biglycan have in atherosclerotic lesion development and progression. In addition to standard atherosclerotic lesion analysis and extensive histologic characterization including immunohistochemistry for different collagen types and biglycan, intravital microscopy and magnetic resonance imaging will be used to characterize the vascular pathology in these mice. Overall, these proposed studies will more clearly define the role biglycan accumulation and biglycan GAG modification have in the pathogenesis of atherosclerosis.
这个子项目是许多研究子项目中的一个
由NIH/NCRR资助的中心赠款提供的资源。子项目和
研究者(PI)可能从另一个NIH来源获得了主要资金,
因此可以在其他CRISP条目中表示。所列机构为
研究中心,而研究中心不一定是研究者所在的机构。
本研究的目的是探讨硫酸软骨素(CS)和硫酸皮肤素(DS)蛋白多糖生物合成在动脉粥样硬化形成中的作用。随着动脉粥样硬化病变在血管壁中的发展,CS和DS蛋白聚糖双糖蛋白聚糖、核心蛋白聚糖和多功能蛋白聚糖积累。因为脂蛋白在体外与
蛋白聚糖的生物合成增加并与它们共定位在动脉粥样硬化病变中,已经假设血管壁中细胞的蛋白聚糖生物合成增加是致动脉粥样硬化的。双糖蛋白聚糖是用于结合和保留脂蛋白的可能的候选蛋白聚糖,因为它在体外结合致动脉粥样硬化脂蛋白,在人动脉粥样硬化病变中与载脂蛋白B(apoB)和E(apoE)共定位,并且在小鼠病变中与apoB和apoE比核心蛋白聚糖更紧密地共定位。此外,由于双糖链具有蛋白质和糖胺聚糖(GAG)介导的与其他蛋白质(例如胶原蛋白、脂蛋白、TGF β)的相互作用,我们假设这些相互作用对血管壁中病变的结构和发展是重要的。 为了验证这些假设,我们的三个目标集中在测量和表征3种动物模型中的动脉粥样硬化。在具体目标1中,我们将确定内皮细胞生物合成双糖链蛋白聚糖的增加是否会加剧动脉粥样硬化的发展。在具体目标2中,我们将确定血管平滑肌细胞生物合成双糖链蛋白聚糖的增加是否会加剧动脉粥样硬化的发展。在具体目标3中,我们将确定双糖链蛋白聚糖的GAG修饰对于动脉粥样硬化病变的发展和结构是否重要。所有三种小鼠模型将通过将它们与低密度脂蛋白受体缺陷或载脂蛋白E缺陷小鼠杂交来产生致动脉粥样硬化性。我们的目的是用这些小鼠动脉粥样硬化模型来确定双糖链蛋白聚糖的生物合成增加和GAG修饰在动脉粥样硬化病变发展和进展中的作用。除了标准动脉粥样硬化病变分析和广泛的组织学表征(包括不同胶原类型和双糖链蛋白聚糖的免疫组织化学)外,还将使用活体显微镜和磁共振成像来表征这些小鼠的血管病理学。总之,这些拟议的研究将更清楚地定义双糖链聚糖积累和双糖链聚糖GAG修饰在动脉粥样硬化发病机制中的作用。
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 }}
MYRON E HINSDALE其他文献
MYRON E HINSDALE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('MYRON E HINSDALE', 18)}}的其他基金
Extracellular determinants of polycystic kidney disease severity
多囊肾病严重程度的细胞外决定因素
- 批准号:
8681434 - 财政年份:2010
- 资助金额:
$ 25.08万 - 项目类别:
Extracellular determinants of polycystic kidney disease severity
多囊肾病严重程度的细胞外决定因素
- 批准号:
8479351 - 财政年份:2010
- 资助金额:
$ 25.08万 - 项目类别:
Extracellular determinants of polycystic kidney disease severity
多囊肾病严重程度的细胞外决定因素
- 批准号:
8115217 - 财政年份:2010
- 资助金额:
$ 25.08万 - 项目类别:
Extracellular determinants of polycystic kidney disease severity
多囊肾病严重程度的细胞外决定因素
- 批准号:
7868503 - 财政年份:2010
- 资助金额:
$ 25.08万 - 项目类别:
Extracellular determinants of polycystic kidney disease severity
多囊肾病严重程度的细胞外决定因素
- 批准号:
8298637 - 财政年份:2010
- 资助金额:
$ 25.08万 - 项目类别:
COBRE: OK MED RES FOUND: P5: ROLE OF PROTEOGLYCAN IN ATHEROGENESIS
COBRE:确定医学研究结果:P5:蛋白聚糖在动脉粥样硬化中的作用
- 批准号:
8168453 - 财政年份:2010
- 资助金额:
$ 25.08万 - 项目类别:
COBRE: OK MED RES FOUND: P5: ROLE OF PROTEOGLYCAN IN ATHEROGENESIS
COBRE:确定医学研究结果:P5:蛋白聚糖在动脉粥样硬化中的作用
- 批准号:
7382048 - 财政年份:2006
- 资助金额:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 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:
$ 25.08万 - 项目类别:
Grant-in-Aid for Early-Career Scientists