Senescence dysregulates of inflammation-resolution programs in atherosclerosis
动脉粥样硬化炎症消退程序的衰老失调
基本信息
- 批准号:10629852
- 负责人:
- 金额:$ 5.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-15 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcetylationAcuteAreaArterial Fatty StreakAtherosclerosisBlocking AntibodiesCancer PatientCardiovascular DiseasesCause of DeathCell AgingCell Cycle ArrestCell physiologyCellsChronicDataDietDinoprostoneEatingEnzymesEquilibriumEtiologyEventExhibitsGlycolysisHumanImpairmentIn VitroIndustrializationInflammationInflammatoryInflammatory ResponseKnowledgeLesionLeukotrienesLinkLipoxinsMediatingMediator of activation proteinModelingMusMyelogenousMyeloid CellsNecrosisPTGS2 genePhenotypeProcessProductionProstaglandinsRadiationRegulationResearchResolutionSeriesSignal PathwaySignal TransductionSurfaceTestingWorkbasecardiovascular disorder riskdriving forcehypercholesterolemiaimprovedin vivoinsightmouse modelnovelpreventprogramspublic health prioritiesrestorationsenescencetissue injurytissue repairtreatment strategy
项目摘要
Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the industrialized world. Failed
resolution of a chronic inflammatory response is an important driving force in the progression of
atherosclerosis. Resolution is mediated by the critical balance between specialized pro-resolving mediators
(SPMs) such as lipoxins and resolvins and pro-inflammatory factors like leukotrienes (LTs) and prostaglandins
(PGs). Previous work from our lab and others suggest that SPMs are defectively synthesized in plaques and
that restoration of SPMs prevents atherosclerosis progression in mice. Gaps remain in our understanding as to
a) what cellular processes derange the synthesis of SPMs in
protective actions of SPMs in atherosclerosis. Therefore, the
plaques and b) mechanisms associated with the
overall objective of this proposal is to understand
new mechanisms of dysregulated resolution in atherosclerosis and to harness new SPM signaling pathways
towards a novel treatment strategy. Cellular senescence is an irreversible cell cycle arrest that leads to a highly
pro-inflammatory phenotype called the senescence-associated secretory phenotype (SASP). Prominent
features of senescent cells (SCs) include elevated levels of COX2 and PGs and heightened glycolysis. SCs
recently emerged as a driver of plaque necrosis but mechanisms are poorly understood. Our new work
suggests that senescence impairs endogenous resolution programs and that key SPMs can limit the SASP.
We proposed a series of studies to identify the mechanisms associated with senescence and impaired
resolution (Aim I), the link between myeloid senescent cells and SPM formation in plaques (Aim II) and
mechanisms underlying how hypercholesterolemia impacts senescence and SPM synthesis (Aim III). The link
between dysregulated resolution programs and senescence is a completely new and unexplored area of
research that may reveal new treatment strategies for atherosclerosis that are complementary to those that
currently exist.
在工业化国家,动脉粥样硬化性心血管疾病(CVD)是导致死亡的主要原因。失败的
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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Gabrielle Fredman其他文献
Gabrielle Fredman的其他文献
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{{ truncateString('Gabrielle Fredman', 18)}}的其他基金
Inflammation-resolution impairments in aging and atherosclerosis
衰老和动脉粥样硬化中的炎症消退障碍
- 批准号:
10724859 - 财政年份:2023
- 资助金额:
$ 5.22万 - 项目类别:
Senescence dysregulates of inflammation-resolution programs in atherosclerosis
动脉粥样硬化炎症消退程序的衰老失调
- 批准号:
10427260 - 财政年份:2020
- 资助金额:
$ 5.22万 - 项目类别:
Senescence dysregulates of inflammation-resolution programs in atherosclerosis
动脉粥样硬化炎症消退程序的衰老失调
- 批准号:
10025692 - 财政年份:2020
- 资助金额:
$ 5.22万 - 项目类别:
Senescence dysregulates of inflammation-resolution programs in atherosclerosis
动脉粥样硬化炎症消退程序的衰老失调
- 批准号:
10333044 - 财政年份:2020
- 资助金额:
$ 5.22万 - 项目类别:
Senescence dysregulates of inflammation-resolution programs in atherosclerosis
动脉粥样硬化炎症消退程序的衰老失调
- 批准号:
10631070 - 财政年份:2020
- 资助金额:
$ 5.22万 - 项目类别:
Senescence dysregulates of inflammation-resolution programs in atherosclerosis
动脉粥样硬化炎症消退程序的衰老失调
- 批准号:
10214691 - 财政年份:2020
- 资助金额:
$ 5.22万 - 项目类别:
Senescence dysregulates of inflammation-resolution programs in atherosclerosis
动脉粥样硬化炎症消退程序的衰老失调
- 批准号:
10848738 - 财政年份:2020
- 资助金额:
$ 5.22万 - 项目类别:
Necroptosis Impairs Inflammation-Resolution Programs in Atherosclerosis
坏死性凋亡损害动脉粥样硬化的炎症消退程序
- 批准号:
9496529 - 财政年份:2018
- 资助金额:
$ 5.22万 - 项目类别:
Necroptosis Impairs Inflammation-Resolution Programs in Atherosclerosis
坏死性凋亡损害动脉粥样硬化的炎症消退程序
- 批准号:
10349539 - 财政年份:2018
- 资助金额:
$ 5.22万 - 项目类别:
Specialized pro-resolving mediators in atherosclerosis
动脉粥样硬化的专门促解决介质
- 批准号:
8566813 - 财政年份:2013
- 资助金额:
$ 5.22万 - 项目类别:
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