Mitochondria-Mediated Effects and Therapeutic Potential of Atrial Natriuretic Peptide in Salt-Sensitive Hypertension Diversity Supplement
盐敏感性高血压多样性补充剂中心房钠尿肽的线粒体介导作用和治疗潜力
基本信息
- 批准号:10337412
- 负责人:
- 金额:$ 2.7万
- 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:2020-08-14 至 2021-07-31
- 项目状态:已结题
- 来源:
- 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
项目摘要
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.
项目摘要
对于血压盐敏感性患者亚群,目前尚无特异性治疗方法
(BP)不幸的是,盐敏感性的分子机制仍然知之甚少。之一
盐敏感性(SS)高血压发展的主要机制涉及以下缺陷:
肾脏排泄盐的能力。由Nppa编码的心房利钠肽(ANP)是一种已知的激素,
促进盐分排泄和降低血压。有临床数据表明,
SS高血压的发展。在其他作用中,已知ANP(通过cGMP相关机制)是
有益于线粒体生物能量学和生物发生。然而,在知识方面存在差距,
ANP对肾脏线粒体的影响,尤其是在SS高血压中。我们的总体假设是
母项目是在SS高血压中,ANP缺乏/对ANP敏感性降低是肾损害的原因,
线粒体功能障碍和相关的钠转运失衡。要解决的中心假设的
根据这一建议,我们制定了三个具体目标:目标1。确定增加ANP水平是否有益
用于SS高血压的肾盐处理和心脏功能。目标二。确定肾cGMP水平是否低
由于缺乏ANP导致肾线粒体Ca 2+和活性氧(ROS)增加。
目标3。测试功能障碍性细胞破坏Ca 2+平衡和过量ROS产生的假设。
线粒体影响SS高血压肾钠处理。从这些提出的目标博士斯皮尔斯和博士。
Ilatovskaya得出的其他目的集中在研究在SS高血压的背景下ANP的作用。
肾小球功能和损伤。这一补充项目的重点目标如下:
补编目标1.探讨心钠素(ANP)对SS肾小球功能和损伤的生理作用
高血压补充目标2。分析Nppa基因敲除对足细胞钙处理的影响,
线粒体功能在SS高血压中的作用Spires博士和Ilatovskaya博士组建了一个非常强大的团队,
导师和合作者,以帮助完成这些目标,以及斯皮尔斯博士的方法培训期间,
该补充方案将与严格的职业发展方案相结合。圆满完成
主提案中的拟议研究以及本补充奖的拟议研究将
解开盐敏感性的新的因果机制。
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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Daria Ilatovskaya其他文献
Daria Ilatovskaya的其他文献
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{{ truncateString('Daria Ilatovskaya', 18)}}的其他基金
Improving awareness of women with hypertension: ROAR (Rural, Obese, At Risk) Career Enhancement Core
提高女性高血压患者的意识:ROAR(农村、肥胖、高危)职业提升核心
- 批准号:
10714535 - 财政年份:2023
- 资助金额:
$ 2.7万 - 项目类别:
Mitochondria-mediated effects and therapeutic potential of Atrial Natriuretic Peptide in salt-sensitive hypertension
心房钠尿肽在盐敏感性高血压中的线粒体介导作用和治疗潜力
- 批准号:
10676800 - 财政年份:2020
- 资助金额:
$ 2.7万 - 项目类别:
Mitochondria-mediated effects and therapeutic potential of Atrial Natriuretic Peptide in salt-sensitive hypertension
心房钠尿肽在盐敏感性高血压中的线粒体介导作用和治疗潜力
- 批准号:
10442162 - 财政年份:2020
- 资助金额:
$ 2.7万 - 项目类别:
Mitochondria-mediated effects and therapeutic potential of Atrial Natriuretic Peptide in salt-sensitive hypertension
心房钠尿肽在盐敏感性高血压中的线粒体介导作用和治疗潜力
- 批准号:
10472035 - 财政年份:2020
- 资助金额:
$ 2.7万 - 项目类别:
The involvement of ATP-dependent inhibition of ENaC in ARPKD cystogenesis
ENaC 的 ATP 依赖性抑制参与 ARPKD 囊肿发生
- 批准号:
10419229 - 财政年份:2018
- 资助金额:
$ 2.7万 - 项目类别:
The involvement of ATP-dependent inhibition of ENaC in ARPKD cystogenesis
ENaC 的 ATP 依赖性抑制参与 ARPKD 囊肿发生
- 批准号:
9146873 - 财政年份:2015
- 资助金额:
$ 2.7万 - 项目类别:
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