Pathophysiological Activities of Oxidized Phospholipids
氧化磷脂的病理生理活性
基本信息
- 批准号:8432820
- 负责人:
- 金额:$ 33.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-04-01 至 2014-11-03
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAffinityAgonistArterial Fatty StreakAtherosclerosisBindingBiological AssayBlocking AntibodiesBlood CirculationBlood ClotBlood PlateletsBlood coagulationCD36 geneCellsCholesterolCytoplasmic GranulesDataDevelopmentDiabetes MellitusDiseaseDyslipidemiasElementsFamilyFunctional disorderGenerationsHyperlipidemiaIn VitroInvestigationLecithinLigandsMediatingMetabolic syndromeMolecularMusOxidative StressPattern RecognitionPhasePhospholipase A2PhospholipidsPhysiologicalPlatelet ActivationPlayPropertyProteinsReceptor CellRecombinantsRegulationRiskRisk FactorsRoleRuptureSR-B proteinsSR-BI receptorSignal TransductionSiteSolidStagingTestingThrombosisToll-like receptorsUp-Regulationacute coronary syndromeadductin vivomacrophagenoveloverexpressionoxidized lipidreceptorreceptor functionresponsescavenger receptorsensor
项目摘要
A significant role for increased platelet reactivity in the pathophysiology of occlusive
arterial thrombosis is widely recognized. However, the mechanisms responsible for
enhancing platelet reactivity in vivo during hyperlipidemia are poorly understood. We
have recently isolated and structurally defined a novel family of oxidized choline
glycerophospholipids (oxPCCD36) that are present in vivo at sites of enhanced oxidative
stress. oxPCCD36 serve as high affinity ligands for scavenger receptors class B and
modulate platelet reactivity and thrombosis in oxidative stress. Our preliminary studies
demonstrated that a class of products formed as a result of degradation of oxPCCD36 by
PLA2 (carboxyalkylpyrolle protein adducts) is a new and powerful platelet agonist,
however, the receptors mediating its effect are not known. Platelets express a number of
receptors with pattern recognition properties, including several toll like receptors (TLRs).
A recent study suggested that platelet TLRs may modulate thrombosis when their
ligands are present in circulation. This proposal will address the hypothesis that platelet
TLRs alone, or in cooperation with scavenger receptors modulate platelet reactivity and
prothrombotic state induced by endogenous ligands generated in oxidative stress. This
proposal will also pursue the hypothesis that carboxyalkylpyrolle protein adducts serve
as novel ligands for platelet scavenger /toll like receptors and identify the mechanisms of
prothrombotic activity. Finally, we will continue the investigation of the molecular
mechanism of scavenger receptor BI regulation of platelet function and thrombosis in
dyslipidemia. Our preliminary data strongly support our hypothesis.
The Specific Aims are:
Aim1: To assess whether the platelet activating and prothrombotic activities of oxPCCD36
are mediated by platelet TLRs alone, or in cooperation with scavenger receptors class B.
Aim2: To investigate the role of scavenger receptor-BI in platelet function in
dyslipidemia and oxidative stress.
Aim3: To elucidate the mechanism and assess the physiological and pathophysiological
consequences of the interaction between carboxyalkylpyrolle protein adducts (CAPs)
and platelets.
血小板反应性增高在闭塞性病理生理中的重要作用
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)
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EUGENE A PODREZ其他文献
EUGENE A PODREZ的其他文献
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{{ truncateString('EUGENE A PODREZ', 18)}}的其他基金
Mechanism of atheroprotective function of Akt3 kinase
Akt3激酶的动脉粥样硬化保护功能机制
- 批准号:
8858363 - 财政年份:2015
- 资助金额:
$ 33.29万 - 项目类别:
Mechanism of atheroprotective function of Akt3 kinase
Akt3激酶的动脉粥样硬化保护功能机制
- 批准号:
9031810 - 财政年份:2015
- 资助金额:
$ 33.29万 - 项目类别:
Mechanism of atheroprotective function of Akt3 kinase
Akt3激酶的动脉粥样硬化保护功能机制
- 批准号:
9414577 - 财政年份:2015
- 资助金额:
$ 33.29万 - 项目类别:
Pathophysiological Activities of Oxidized Phospholipids
氧化磷脂的病理生理活性
- 批准号:
7840709 - 财政年份:2009
- 资助金额:
$ 33.29万 - 项目类别:
Pathophysiological Activities of Oxidized Phospholipids
氧化磷脂的病理生理活性
- 批准号:
7195835 - 财政年份:2005
- 资助金额:
$ 33.29万 - 项目类别:
Pathophysiological Activities of of Oxidized Phospholipids
氧化磷脂的病理生理活性
- 批准号:
8962155 - 财政年份:2005
- 资助金额:
$ 33.29万 - 项目类别:
Pathophysiological Activities of of Oxidized Phospholipids
氧化磷脂的病理生理活性
- 批准号:
9171370 - 财政年份:2005
- 资助金额:
$ 33.29万 - 项目类别:
Pathophysiological Activities of Oxidized Phospholipids
氧化磷脂的病理生理活性
- 批准号:
7367193 - 财政年份:2005
- 资助金额:
$ 33.29万 - 项目类别:
Pathophysiological Activities of Oxidized Phospholipids
氧化磷脂的病理生理活性
- 批准号:
6925309 - 财政年份:2005
- 资助金额:
$ 33.29万 - 项目类别:
Pathophysiological Activities of Oxidized Phospholipids
氧化磷脂的病理生理活性
- 批准号:
7031657 - 财政年份:2005
- 资助金额:
$ 33.29万 - 项目类别:
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