Inflammation, HDL and class B Scavenger Rectors
Inflammation, HDL and class B Scavenger Rectors
批准号:
7219727
负责人:
Deneys Rem Van Der Westhuyzen
金额:
$30.14万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2006
资助国家:
美国
项目状态:
已结题
起止时间:
2006-12-01 至 2011-11-30
关键词:
AcuteAcute-Phase ProteinsAcute-Phase ReactionAffinityApolipoproteinsArterial Fatty StreakAtherosclerosisCD36 geneCardiovascular DiseasesCatabolismCellsCharacteristicsCholesterolChronicClassExhibitsHepatocyteHigh Density Lipoprotein CholesterolHigh Density LipoproteinsInflammationInflammatoryInflammatory ResponseLipidsLipopolysaccharidesLiverMediatingMediator of activation proteinMetabolismModificationPathway interactionsPeripheralPhasePhospholipasePlayPost-Translational Protein ProcessingProcessProteinsRecyclingResearch PersonnelRiskRoleSR-B proteinsSerum amyloid A proteinStructureTestingWestern Worldmacrophagemortalityprogramsprotective effectreceptorreverse cholesterol transporttherapeutic targettraffickinguptake
中文摘要
动脉粥样硬化是西方世界死亡的主要原因。高密度脂蛋白的水平是相反的
英文摘要
Atherosclerosis is the leading cause of mortality in the western world. HDL, the levels of which are inversely
correlated with the risk of atherosclerosis, exerts its protective effect in large part through its ability to
mobilize cholesterol from peripheral cells and to stimulate reverse cholesterol transport to the liver.
Atherosclerosis and inflammation share many common features and the atherosclerotic process exhibits
characteristics of chronic inflammation. Inflammation significantly alters HDL structure, composition and
levels, but the underlying mechanisms and the consequences of such modifications are not understood. In
studying the impact of HDL on atherosclerosis it is therefore critical to understand how such HDL
modifications, that can result both systemically and within the microenvironment of the atherosclerotic lesion,
influence HDL metabolism and its role in cholesterol transport. Inflammatory modifications in HDL may also
alter the protective effect of HDL in neutralizing the inflammatory effects of bacterial lipopolysaccharides.
Inflammation and the acute-phase response results in a marked induction of acute phase proteins including
serum amyloid A (SAA), which becomes a major HDL apolipoprotein. Recently, we identified two Class B
scavenger receptors, SR-BI and CD36, as high-affinity receptors for SAA and also showed that SAA
promotes cellular cholesterol efflux. Further, SR-BI and CD36 were shown to efficiently take up SAA into
cells, a process that may be important in the function and metabolism of SAA. In this proposal we will
examine the overall hypothesis that HDL cholesterol transport by Class B scavenger receptors is significantly
altered during inflammation through the effects of acute phase proteins and modifications in HDL structure.
Aim 1 will examine the hypothesis that the Class B scavenger receptors mediate the cellular uptake and
catabolism of SAA. Studies will investigate the roles of SR-BI and CD36 in the cellular uptake, recycling and
degradation of SAA in hepatocytes and macrophages. Aim 2 will determine how SAA and HDL remodeling
during inflammation impacts HDL cholesterol transport by Class B scavenger receptors. Studies will
investigate how SAA and acute phase modifications of HDL influence SR-BI-dependent cholesterol efflux
from hepatocytes and macrophages and SR-BI-mediated selective lipid uptake into hepatocytes. Aim 3 will
test the hypothesis that Class B scavenger receptors and SAA regulate the LPS-induced inflammatory
response. Studies will examine the roles of SR-BI and CD36 in LPS- and LTA-induced inflammation and the
modulating effects of SAA. These studies are expected to provide greater understanding of how
inflammation influences the protective function of HDL.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Class B Scavenger Receptors and Atherosclerosis
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批准号:7798400
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项目类别:
-
资助金额:$0.0万
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财政年份:2009
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
Class B Scavenger Receptors and Atherosclerosis
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批准号:8391579
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项目类别:
-
资助金额:$0.0万
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财政年份:2009
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
Class B Scavenger Receptors and Atherosclerosis
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批准号:7904139
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项目类别:
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资助金额:$0.0万
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财政年份:2009
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
Class B Scavenger Receptors and Atherosclerosis
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批准号:8195617
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项目类别:
-
资助金额:$0.0万
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财政年份:2009
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
HDL Function and Metabolism During Inflammation
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批准号:7586667
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项目类别:
-
资助金额:$141.24万
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财政年份:2007
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
HDL Function and Metabolism During Inflammation
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批准号:7793418
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项目类别:
-
资助金额:$141.98万
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财政年份:2007
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
HDL Function and Metabolism During Inflammation
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批准号:7184075
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项目类别:
-
资助金额:$147.77万
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财政年份:2007
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
HDL Function and Metabolism During Inflammation
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批准号:7406817
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项目类别:
-
资助金额:$141.63万
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财政年份:2007
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
HDL Function and Metabolism During Inflammation
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批准号:8049664
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项目类别:
-
资助金额:$141.98万
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财政年份:2007
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
Administrative Core
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批准号:7219729
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项目类别:
-
资助金额:$5.68万
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财政年份:2006
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
SR-BI: INFLUENCE OF APOA-II
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批准号:6390556
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项目类别:
-
资助金额:$25.2万
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财政年份:2000
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
CLASS B SCAVENGER RECEPTORS AND FOAM CELL FORMATION
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批准号:6194115
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项目类别:
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资助金额:$22.05万
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财政年份:2000
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
CLASS B SCAVENGER RECEPTORS AND FOAM CELL FORMATION
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批准号:6390893
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项目类别:
-
资助金额:$22.05万
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财政年份:2000
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
SR-BI: INFLUENCE OF APOA-II
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批准号:6527243
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项目类别:
-
资助金额:$25.2万
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财政年份:2000
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
SR-BI: INFLUENCE OF APOA-II
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批准号:6642686
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项目类别:
-
资助金额:$25.2万
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财政年份:2000
-
负责人:Deneys Rem Van Der Westhuyzen
-
依托单位:
SR-BI: INFLUENCE OF APOA-II
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批准号:6193761
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项目类别:
-
资助金额:$25.2万
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财政年份:2000
-
负责人:Deneys Rem Van Der Westhuyzen
-
依托单位:
CLASS B SCAVENGER RECEPTORS AND FOAM CELL FORMATION
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批准号:6656305
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项目类别:
-
资助金额:$22.05万
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财政年份:2000
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
CLASS B SCAVENGER RECEPTORS AND FOAM CELL FORMATION
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批准号:6527650
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项目类别:
-
资助金额:$22.05万
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财政年份:2000
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
SR-BI and SR-BII recycling and selective lipid uptake
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批准号:7471366
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项目类别:
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资助金额:$30.9万
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财政年份:2000
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
SR-BI and SR-BII recycling and selective lipid uptake
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批准号:7114317
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项目类别:
-
资助金额:$31.89万
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财政年份:1999
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负责人:Deneys Rem Van Der Westhuyzen
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依托单位:
海外基金