Cardiomyocyte TRPV4 and Angiotensin-II induced ventricular arrhythmia with aging
Cardiomyocyte TRPV4 and Angiotensin-II induced ventricular arrhythmia with aging
批准号:
10658009
负责人:
Timothy Lee Domeier
金额:
$41.04万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
未结题
起止时间:
2017-03-03 至 2028-03-31
关键词:
AcuteAgingAngiotensin IIArrhythmiaAutopsyBiological AgingBlood PressureBlood VolumeCalciumCalcium SignalingCardiacCardiac MyocytesCardiovascular DiseasesCardiovascular PathologyCardiovascular PhysiologyCationsCause of DeathChronicClinical TrialsCouplingDataEchocardiographyElectrocardiogramElectrophysiology (science)Experimental DesignsFamilyGeneticGoalsHeartHeart HypertrophyHistologicHomeostasisHormonesIncidenceInjectionsIon ChannelIschemiaKnock-outKnowledgeLinkMechanicsMediatorMicroelectrodesModelingMonitorMusMuscle CellsMyocardial ContractionMyocardial InfarctionOsmosisPerfusionPhysiologicalPredispositionPublishingReceptor ActivationReceptor, Angiotensin, Type 1Regional PerfusionReperfusion InjuryReperfusion TherapyResearchRoleSignal TransductionStimulusStressStretchingTRP channelTailTestingVanilloidVeinsVentricularVentricular ArrhythmiaVentricular Remodelingage relatedagedcell typecomorbiditycoronary fibrosisgenetic approachgenetic manipulationheart cellheart damageheart functionin vivoin vivo monitoringinhibitormembernovelosmotic minipumpoverexpressionpeptide hormonepharmacologicpreventprogramsreceptorresponsetherapeutic targettrafficking
中文摘要
项目总结/文摘
英文摘要
Project Summary/Abstract
Transient receptor potential vanilloid, member 4 (TRPV4) is a cation channel highly expressed in cardiomyocytes
with aging, and contributes to enhanced cardiomyocyte calcium cycling and hypercontractility following TRPV4
gating stimuli including osmotic stress and mechanical stretch. Excessive TRPV4 activation leads to cardiac
damage and ventricular arrhythmia. Angiotensin II (AngII) is a peptide hormone critically important to
cardiovascular physiology and pathology due to its regulatory effects on blood volume and pressure. In many
cell types, AngII increases TRPV4 activity although the contribution of this signaling axis to cardiomyocyte
calcium homeostasis is currently unknown. This renewal proposal tests the central hypothesis that TRPV4
contributes to AngII-dependent cardiomyocyte calcium signaling and ventricular arrhythmia. To test this
hypothesis, we will use both a pharmacologic (TRPV4 inhibition) and genetic approach (cardiomyocyte specific
TRPV4 deletion or overexpression) to examine the functional role of TRPV4 in isolated cardiomyocytes, in
isolated perfused hearts, and in mice in vivo. Specific Aim 1 uses isolated cardiomyocytes and isolated perfused
hearts to test the hypothesis that AngII promotes TRPV4 trafficking, increases TRPV4 activity, and enhances
cardiomyocyte calcium transients during excitation-contraction coupling. Specific Aim 2 tests the hypothesis that
cardiomyocyte TRPV4 contributes to AngII-induced cardiac remodeling, and examines the role of TRPV4 in
hypertrophic and fibrotic remodeling following AngII excess (osmotic mini-pumps) and during biological aging.
Specific Aim 3 tests the hypothesis that TRPV4 contributes to pro-arrhythmic cardiomyocyte calcium signals and
ventricular arrhythmia following both acute and chronic AngII excess. The overall goal of this project is to
establish TRPV4 as a therapeutic target to prevent arrhythmia with aging.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Cardiomyocyte TRPV4 and cardiac dysfunction following ischemia-reperfusion in the aged heart.
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批准号:10112289
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项目类别:
-
资助金额:$37.57万
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财政年份:2017
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负责人:Timothy Lee Domeier
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依托单位:
Cardiomyocyte TRPV4 and cardiac dysfunction following ischemia-reperfusion in the aged heart.
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批准号:9280032
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项目类别:
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资助金额:$37.57万
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财政年份:2017
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负责人:Timothy Lee Domeier
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依托单位:
Cardiomyocyte stretch and intracellular calcium release with advancing age
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批准号:8519199
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项目类别:
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资助金额:$11.3万
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财政年份:2012
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负责人:Timothy Lee Domeier
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依托单位:
Cardiomyocyte stretch and intracellular calcium release with advancing age
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批准号:8699626
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项目类别:
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资助金额:$11.3万
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财政年份:2012
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负责人:Timothy Lee Domeier
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依托单位:
Cardiomyocyte stretch and intracellular calcium release with advancing age
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批准号:8383278
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项目类别:
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资助金额:$11.3万
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财政年份:2012
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负责人:Timothy Lee Domeier
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依托单位:
Cardiomyocyte stretch and intracellular calcium release with advancing age
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批准号:8897219
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项目类别:
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资助金额:$10.29万
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财政年份:2012
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负责人:Timothy Lee Domeier
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依托单位:
IP3R-Dependent Signaling in Excitation-Contraction Coupling during Heart Failure
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批准号:7331064
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项目类别:
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资助金额:$2.02万
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财政年份:2007
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负责人:Timothy Lee Domeier
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依托单位:
IP3R-Dependent Signaling in Excitation-Contraction Coupling during Heart Failure
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批准号:7559275
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项目类别:
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资助金额:$2.72万
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财政年份:2007
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负责人:Timothy Lee Domeier
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依托单位:
IP3R-Dependent Signaling in Excitation-Contraction Coupling during Heart Failure
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批准号:7496573
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项目类别:
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资助金额:$4.96万
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财政年份:2007
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负责人:Timothy Lee Domeier
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依托单位:
KCa channels and conducted vasodilation
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批准号:6994292
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项目类别:
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资助金额:$1.99万
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财政年份:2005
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负责人:Timothy Lee Domeier
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依托单位:
海外基金