MIF and Cardiovascular Inflammation
MIF 与心血管炎症
基本信息
- 批准号:10269328
- 负责人:
- 金额:$ 37.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-15 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:5&apos-AMP-activated protein kinaseAcuteAge-YearsAgingAgonistAllelesAnteriorAnterior Descending Coronary ArteryAtherosclerosisBindingBlood VesselsCD44 geneCardiacCardiac MyocytesCardiac Surgery proceduresCardiovascular systemCell RespirationCellsCellular Stress ResponseClinical ResearchComplexCoronary arteryCyclic AMP-Dependent Protein KinasesElderlyEmbryoExerciseFibroblastsGenotypeGoalsHeartHumanImpairmentIncidenceIndividualInflammationInflammatory ResponseInjuryIntegral Membrane ProteinInterventionKnockout MiceLaboratoriesLeadLeftLeukocytesLigationLinkLongevityMigration Inhibitory FactorMolecularMusOlder PopulationOperative Surgical ProceduresOutcomeOxidative StressPathway interactionsPerformancePharmacologyPhenolsPhysical activityPhysiologicalPredispositionPreventionProtein KinaseProtocols documentationReactive Oxygen SpeciesRegulationReportingResistanceRoleSepsisShockSignal PathwaySignal TransductionSourceStressSurgical InjuriesSurgical ShockSystemTestingVascular DiseasesVascular SystemWorkage relatedagedatherothrombosiscoronary angioplastycytokineex vivo perfusionexercise trainingheart damageimprovedin vivomortalitynovelnovel strategiesnovel therapeutic interventionolder patientpopulation basedpreventreceptorresponserestorationsmall moleculevascular inflammationvascular injury
项目摘要
Project Summary
Clinical studies have reported a higher incidence of surgical stress-induced acute injury in the elderly. The
mortality after cardiac surgery, atherosclerosis, sepsis, or coronary angioplasty in patients older than 60 years
of age appears to be related to a decline in intrinsic resistance to surgical stress-related acute injury. The
mechanisms responsible for the atherosclerosis-related vascular intolerance in aging are incompletely
understood and the signaling pathways involved in regulating cellular responses to acute injury related
inflammation arising from surgical stress remain largely unknown. The blocked vessels by atherothrombosis
cause ATP depletion and subsequent AMP accumulation, which activates AMP-activated protein kinase
(AMPK), a central component of the cellular stress response that regulates oxidative metabolism towards ATP
restoration under stress conditions. AMPK regulates pathways that control the oxidative stress-related
vascular inflammation. We have reported that an aging-related reduction in the macrophage migration
inhibitory factor (MIF)-AMPK signaling cascade is an important contributing factor leading to increased
sensitivity to reactive oxygen species (ROS) by surgical ligation of the left anterior descending coronary artery.
Accordingly, we hypothesize that aging is associated with a decline in the ability of vascular cells to render the
MIF-AMPK signaling cascade active in response to inflammation caused by atherosclerosis, thus resulting in
exacerbated vascular injury. We will test this hypothesis in the following specific aims: Aim 1, define the role of
the MIF receptor in age-related impaired AMPK signaling in response to vascular inflammation by oxidative
stress; and Aim 2, evaluate the capability of small-molecule MIF agonist to improve stress-induced MIF-AMPK
activation in the cardiovascular system. In this manner, we seek to advance our understanding of the
mechanisms behind aging-related alterations in cardiac AMPK signaling pathways in response to inflammation
by surgical ligation of the coronary artery. Furthermore, we propose both exercise and a novel pharmacological
strategy aimed at ameliorating oxidative stress-induced vascular inflammation that occurs in the older
population.
项目总结
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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Ji Li其他文献
Ji Li的其他文献
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{{ truncateString('Ji Li', 18)}}的其他基金
A Stress Inducible Protein Sestrin2 in Heart Failure
心力衰竭中的应激诱导蛋白 Sestrin2
- 批准号:
10616476 - 财政年份:2022
- 资助金额:
$ 37.38万 - 项目类别:
A Stress Inducible Protein Sestrin2 in Heart Failure
心力衰竭中的应激诱导蛋白 Sestrin2
- 批准号:
10363811 - 财政年份:2022
- 资助金额:
$ 37.38万 - 项目类别:
A Stress Inducible Protein Sestrin2 in Heart Failure
心力衰竭中的应激诱导蛋白 Sestrin2
- 批准号:
11002402 - 财政年份:2022
- 资助金额:
$ 37.38万 - 项目类别:
Activated Protein C and Cardiac Inflammatory Response
活化蛋白 C 与心脏炎症反应
- 批准号:
10393231 - 财政年份:2018
- 资助金额:
$ 37.38万 - 项目类别:
Activated Protein C and Cardiac Inflammatory Response
活化蛋白 C 与心脏炎症反应
- 批准号:
10004784 - 财政年份:2018
- 资助金额:
$ 37.38万 - 项目类别:
AMPK-SIRT1 Signaling in the Adaptive Metabolic Response
适应性代谢反应中的 AMPK-SIRT1 信号传导
- 批准号:
9114282 - 财政年份:2015
- 资助金额:
$ 37.38万 - 项目类别:
AMPK-SIRT1 Signaling in the Adaptive Metabolic Response
适应性代谢反应中的 AMPK-SIRT1 信号传导
- 批准号:
9243202 - 财政年份:2015
- 资助金额:
$ 37.38万 - 项目类别:
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