Mitochondria-Mediated Effects and Therapeutic Potential of Atrial Natriuretic Peptide in Salt-Sensitive Hypertension Diversity Supplement
Mitochondria-Mediated Effects and Therapeutic Potential of Atrial Natriuretic Peptide in Salt-Sensitive Hypertension Diversity Supplement
批准号:
10337412
负责人:
Daria Ilatovskaya
金额:
$2.7万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-08-14 至 2021-07-31
关键词:
AddressAdipose tissueAffectAnimalsApoptosisAtrial Natriuretic FactorAwardBioenergeticsBiogenesisBlood PressureCalciumClinical DataCyclic GMPDahl Hypertensive RatsDefectDevelopmentEquilibriumEventExcretory functionExhibitsFiltrationGoalsGrantHeart failureHomeostasisHormonesHypertensionInjuryKidneyKidney GlomerulusKnock-outKnowledgeLinkMediatingMentorsMethodologyMitochondriaMolecularMuscleNatriuretic PeptidesOrganOxidative StressParentsPathologicPatientsPeer ReviewPhysiologicalPlasmaProductionProgram DevelopmentRattusReactive Oxygen SpeciesResearchRiskRoleSeveritiesSodiumSodium ChlorideSystemTestingTherapeuticTimeTrainingVasodilationWorkblood pressure reductioncareer developmentdietary saltexperienceglomerular functionheart functionhigh salt diethypertension treatmentmitochondrial dysfunctionnovelparent grantparent projectpatient subsetspodocyterenal damagesalt intakesalt sensitivesalt sensitive hypertensiontreatment strategy
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
There is no specific treatment available for the subpopulation of patients with salt sensitivity of blood pressure
(BP); unfortunately, the molecular mechanisms underlying salt-sensitivity remain poorly understood. One of the
major proposed mechanisms for the development of salt-sensitive (SS) hypertension involves a defect in the
ability of the kidneys to excrete salt. Atrial Natriuretic Peptide (ANP) encoded by Nppa, is a hormone known to
promote salt excretion and BP reduction. There are clinical data implicating inherently low levels of ANP in the
development of SS hypertension. Among other effects, ANP (via cGMP-related mechanisms) is known to be
beneficial for mitochondrial bioenergetics and biogenesis. However, there is a gap in knowledge regarding the
effects of ANP on mitochondria in the kidney, especially in SS hypertension. Our overarching hypothesis of the
parent project is that in SS hypertension ANP deficiency/reduced sensitivity to ANP is causative to renal
mitochondrial dysfunction and associated sodium transport imbalance. To address the central hypothesis of the
parent proposal, we developed three specific aims: Aim 1. Establish whether increased ANP levels are beneficial
for renal salt handling and cardiac function in SS hypertension. Aim 2. Determine whether low renal cGMP level
resulting from lack of ANP causes an increase in renal mitochondrial Ca2+ and reactive oxygen species (ROS).
Aim 3. Test the hypothesis that disrupted Ca2+ balance and excessive ROS production by dysfunctional
mitochondria affect renal sodium handling in SS hypertension. From these proposed aims Dr. Spires and Dr.
Ilatovskaya derived additional aims focused on studying the effects of ANP in SS hypertension in the context of
glomerular function and injury specifically. For the focus of this supplemental project the aims are as follows:
Suppl. Aim 1. To determine the physiological effects of ANP on glomerular function and injury in SS
hypertension. Suppl. Aim 2. To analyze the effects of Nppa knockout on podocyte calcium handling and
mitochondrial function in SS hypertension. Dr. Spires and Dr. Ilatovskaya put together a very strong team of
mentors and collaborators to aid in completion of these Aims, and the methodological training of Dr. Spires during
the Supplement will be combined with a rigorous career development program. The successful completion of
the proposed studies in the parent proposal as well as the those proposed for this supplemental award will
unravel the novel cause-effect mechanisms of salt-sensitivity.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:10714535
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项目类别:
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资助金额:$45.11万
-
财政年份:2023
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负责人:Daria Ilatovskaya
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依托单位:
Mitochondria-mediated effects and therapeutic potential of Atrial Natriuretic Peptide in salt-sensitive hypertension
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批准号:10676800
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项目类别:
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资助金额:$52.54万
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负责人:Daria Ilatovskaya
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依托单位:
Mitochondria-mediated effects and therapeutic potential of Atrial Natriuretic Peptide in salt-sensitive hypertension
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批准号:10442162
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项目类别:
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资助金额:$56.94万
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负责人:Daria Ilatovskaya
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依托单位:
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批准号:10472035
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项目类别:
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资助金额:$52.54万
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负责人:Daria Ilatovskaya
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依托单位:
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批准号:10419229
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项目类别:
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资助金额:$2.11万
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财政年份:2018
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负责人:Daria Ilatovskaya
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依托单位:
The involvement of ATP-dependent inhibition of ENaC in ARPKD cystogenesis
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批准号:9146873
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项目类别:
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资助金额:$8.82万
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财政年份:2015
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负责人:Daria Ilatovskaya
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依托单位:
海外基金