Effect of Oxidized Lipids on Endothelial Migration and Vascular Graft Healing
氧化脂质对内皮迁移和血管移植物愈合的影响
基本信息
- 批准号:7500876
- 负责人:
- 金额:$ 5.13万
- 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:2007-09-01 至 2009-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcuteAddressAffectAgonistAntioxidantsAortaAreaArterial InjuryBindingBlood VesselsBypassCalcium ChannelCaliberCell ProliferationCell physiologyCellsDataDepositionDevelopmentDietDisruptionDown-RegulationEndothelial CellsEnvironmentExtracellular MatrixFocal AdhesionsForeign BodiesFunctional disorderGene ExpressionGoalsHealedHumanHyperplasiaIn VitroInfiltrationInflammationInjuryLaboratoriesLeadLearningLigandsLipidsLiteratureLow Density Lipoprotein oxidationLysophosphatidylcholinesMembrane FluidityMethodsModificationNAD(P)H oxidaseNuclearOralOryctolagus cuniculusOxidative StressPeroxisome Proliferator-Activated ReceptorsPhospholipidsProcessProductionPropertyProsthesisReactive Oxygen SpeciesReconstructive Surgical ProceduresResearchRoleSmooth Muscle MyocytesSystemTestingTransplanted tissueVascular Graftbasecell motilitycytokinegraft failuregraft healinghealinghypercholesterolemiaimprovedin vivolipid metabolismlow density lipoprotein inhibitormacrophagemigrationoxidationoxidized lipidoxidized low density lipoproteinpreventprotein kinase C-deltareceptor expressiontranscription factor
项目摘要
DESCRIPTION (provided by applicant): Prosthetic grafts are used widely in vascular reconstructive surgery, but their long-term patency is limited, in part due to altered cell function caused by oxidized low density lipoprotein (oxLDL). We have shown that: 1) graft material stimulates monocytic cells to oxidize LDL in vitro, 2) this oxLDL inhibits endothelial cell (EC) migration in vitro, 3) explanted grafts contain significantly more lipid oxidation products than the adja- cent aorta, and 4) hypercholesterolemia leads to reduced EC migration onto grafts in rabbits. We also have preliminary data that lysophosphatidylcholine (lysoPC), a lipid oxidation product that accounts for most of oxLDL's inhibitory activity, decreases the level of the nuclear transcription factor peroxisome proliferator- activated receptor y (PPARy), and that PPARy ligands preserve EC migration in lysoPC. Based on these data, we propose as a hypothesis that specific lipid oxidation products that accumulate within synthetic vascular grafts inhibit PPARy allowing continued inflammation and production of reactive oxygen species (ROS) contributing to the inhibition of EC migration, thereby limiting endothelialization of prosthetic grafts in vivo. The goals of this project are to determine the effect of oxLDL and lysoPC on PPAR expression and activity and the effect of PPARs on EC migration in vitro and in vivo. To test our hypothesis, we will determine the effect of oxLDL and lysoPC on PPARa and PPARy expression and activity in EC in vitro and explore mechanisms by which PPAR ligands preserve EC migra- tion in the presence of lipid oxidation products, specifically their effect on lysoPC-induced ROS production. We will investigate the effect of PPARs on graft healing in vivo, comparing PPARa and PPARy expression in ePTFE grafts and normal aorta in rabbits on regular chow and hypercholesterolemic diets, and assess the effect of PPARy ligand on EC ingrowth in ePTFE grafts in these rabbits. The proposed studies will investigate the role of lipid oxidation products in the limited endothelialization of synthetic vascular grafts. Studies will also address the efficacy of PPARy ligands to promote EC healing in vivo. This will lead to a better understanding of the role of lipids in the pathobiology of graft failure, and ultimately, to methods promoting endothelialization of prosthetic grafts and prolonging patency of small- diameter conduits. Lay summary: The goal of our research is to learn more about why bypass grafts fail and ways to prevent it. Specifically, we will study why the cells that normally line blood vessels fail to cover synthetic bypass grafts.
描述(由申请人提供):假体移植物广泛应用于血管重建手术,但其长期开放受到限制,部分原因是氧化低密度脂蛋白(oxLDL)引起的细胞功能改变。我们已经证明:1)移植物材料在体外刺激单核细胞氧化LDL, 2)这种oxLDL在体外抑制内皮细胞(EC)的迁移,3)外植移植物比辅助主动脉含有更多的脂质氧化产物,4)高胆固醇血症导致EC迁移到移植物上的减少。我们也有初步的数据表明,溶血磷脂酰胆碱(lysoPC),一种脂质氧化产物,占oxLDL抑制活性的大部分,降低核转录因子过氧化物酶体增殖体激活受体y (PPARy)的水平,并且PPARy配体在lysoPC中保持EC迁移。基于这些数据,我们提出了一个假设,即合成血管移植物中积累的特定脂质氧化产物抑制PPARy,允许持续的炎症和活性氧(ROS)的产生,从而抑制EC的迁移,从而限制体内假体移植物的内皮化。本项目的目的是确定oxLDL和lysoPC对PPAR表达和活性的影响,以及PPAR对EC在体外和体内迁移的影响。为了验证我们的假设,我们将确定oxLDL和lysoPC对体外EC中PPARa和PPARy表达和活性的影响,并探索PPAR配体在脂质氧化产物存在下保持EC迁移的机制,特别是它们对lysoPC诱导的ROS产生的影响。我们将在体内研究ppar对移植物愈合的影响,比较正常饮食和高胆固醇饮食家兔ePTFE移植物和正常主动脉中PPARa和pparty的表达,并评估pparty配体对ePTFE移植物EC长入的影响。拟议的研究将探讨脂质氧化产物在合成血管移植物有限内皮化中的作用。研究还将探讨pparty配体在体内促进EC愈合的功效。这将使我们更好地理解脂质在移植物衰竭病理生物学中的作用,并最终找到促进假体移植物内皮化和延长小直径导管通畅的方法。摘要:我们研究的目的是更多地了解旁路移植失败的原因和预防方法。具体来说,我们将研究为什么通常排列在血管上的细胞不能覆盖合成旁路移植物。
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 }}
Michael Aaric Rosenbaum其他文献
Michael Aaric Rosenbaum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('Michael Aaric Rosenbaum', 18)}}的其他基金
Endothelial Healing is Inhibited by Activation of TRPC6 Channels
TRPC6 通道的激活会抑制内皮愈合
- 批准号:
10369226 - 财政年份:2022
- 资助金额:
$ 5.13万 - 项目类别:
Endothelial Healing is Inhibited by Activation of TRPC6 Channels
TRPC6 通道的激活会抑制内皮愈合
- 批准号:
10526285 - 财政年份:2022
- 资助金额:
$ 5.13万 - 项目类别:
Endothelial Healing is Inhibited by PI3 Kinase-Induced Activation of TRPC6
PI3 激酶诱导的 TRPC6 激活抑制内皮愈合
- 批准号:
10265334 - 财政年份:2017
- 资助金额:
$ 5.13万 - 项目类别:
Endothelial Healing is Inhibited by PI3 Kinase-Induced Activation of TRPC6
PI3 激酶诱导的 TRPC6 激活抑制内皮愈合
- 批准号:
9240762 - 财政年份:2017
- 资助金额:
$ 5.13万 - 项目类别:
Effect of Oxidized Lipids on Endothelial Migration and Vascular Graft Healing
氧化脂质对内皮迁移和血管移植物愈合的影响
- 批准号:
7328918 - 财政年份:2007
- 资助金额:
$ 5.13万 - 项目类别:
相似海外基金
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 5.13万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 5.13万 - 项目类别:
Operating Grants