GP130 Antagonism in Porcine RV Pressure Overload
GP130 在猪 RV 压力过载中的拮抗作用
基本信息
- 批准号:10616614
- 负责人:
- 金额:$ 67.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAnimal ModelArchitectureAttenuatedBiologyBlood capillariesCalciumCardiacCardiac MyocytesCell NucleusCessation of lifeChemicalsChimeric ProteinsColchicineDataDiseaseDoseEquilibriumFailureFamily suidaeFunctional disorderFutureGenetic TranscriptionGenus HippocampusGrantHumanIL6ST geneIn VitroInflammatoryInterleukin-6LeftLungMeasuresMediatingMedicalMembrane ProteinsMetabolicMetabolic dysfunctionMetabolismMicrotubule StabilizationMicrotubule stabilizing agentMicrotubulesMitochondriaModelingMolecularMolecular ProbesMonocrotalineMorphologyNeurologicPaclitaxelPathologicPathway interactionsPatientsPhosphorylationPhysiologic intraventricular pressurePhysiologicalPhysiologyProteinsPulmonary Vascular ResistancePulmonary vesselsRattusRegulationRight Ventricular DysfunctionRight Ventricular FunctionRight ventricular structureRisk FactorsRodentSeveritiesSignal TransductionStat3 proteinStructureTestingTherapeuticTranslationsTransmission Electron MicroscopyVascular DiseasesVentricularWestern BlottingWorkloadantagonistcardiac magnetic resonance imagingcytokinedensitydruggable targeteffective therapyfirst-in-humangastrointestinalhuman diseasehuman studyimprovedjunctophilinmetabolomicsmortalitynew therapeutic targetpharmacologicporcine modelpre-clinicalpressurepreventpulmonary arterial hypertensionpulmonary arterial pressurereceptorright ventricular failureside effectsmall moleculetargeted treatmenttherapeutic targettraffickingtranslational approach
项目摘要
Project Summary
Pulmonary arterial hypertension (PAH) is a lethal disease with a median survival of only 5-7 years.
Pathophysiologically, PAH is a progressive vasculopathy of the precapillary pulmonary vessels that increases
pulmonary arterial pressures and pulmonary vascular resistance while reducing pulmonary arterial compliance.
The changes in the pulmonary vasculature augment the work load of the right ventricle, which ultimately results
in right ventricular dysfunction (RVD). The presence of RVD is the greatest risk factor for death in PAH;
however, no current PAH therapies actually target the RV directly. In this proposal, we will investigate the
hypothesis that GP130 activation in RV cardiomyocytes promotes cardiomyocyte dysfunction via microtubule
remodeling which causes t-tubule derangements and mitochondrial metabolic dysfunction. We will use state-
of-the-art approaches to probe the molecular and physiological effects of GP130 antagonism on right
ventricular function in porcine RV failure.
项目摘要
肺动脉高压(PAH)是一种致命性疾病,中位生存期仅为5-7年。
在病理生理学上,PAH是一种进行性毛细血管前血管病变,它增加了
在降低肺动脉顺应性的同时降低肺动脉压和肺血管阻力。
肺血管的变化增加了右心室的工作负荷,最终导致
右室功能不全(RVD)。RVD的存在是PAH死亡的最大危险因素;
然而,目前还没有直接针对RV的PAH疗法。在这项建议中,我们将调查
右室心肌细胞gp130激活通过微管促进心肌细胞功能障碍的假说
导致T管排列紊乱和线粒体代谢功能障碍的重塑。我们将使用国家-
探讨gp130拮抗对右室的分子和生理影响的最新方法
猪右室衰竭时的心功能。
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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Kurt W Prins其他文献
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{{ truncateString('Kurt W Prins', 18)}}的其他基金
GP130 Antagonism in Porcine RV Pressure Overload
GP130 在猪 RV 压力过载中的拮抗作用
- 批准号:
10418136 - 财政年份:2022
- 资助金额:
$ 67.54万 - 项目类别:
Multi-scale Investigation of Sex Differences in Right Ventricular Function via Estrogen-Microtubule Interactions
通过雌激素-微管相互作用对右心室功能性别差异进行多尺度研究
- 批准号:
10439249 - 财政年份:2022
- 资助金额:
$ 67.54万 - 项目类别:
Multi-scale Investigation of Sex Differences in Right Ventricular Function via Estrogen-Microtubule Interactions
通过雌激素-微管相互作用对右心室功能性别差异进行多尺度研究
- 批准号:
10614649 - 财政年份:2022
- 资助金额:
$ 67.54万 - 项目类别:
Mechanisms of Junctophilin-2 Misregulation that contribute to right ventricular dysfunction in pulmonary arterial hypertension
Junctophilin-2 失调导致肺动脉高压右心室功能障碍的机制
- 批准号:
10208937 - 财政年份:2018
- 资助金额:
$ 67.54万 - 项目类别:
Mechanisms of Junctophilin-2 Misregulation that contribute to right ventricular dysfunction in pulmonary arterial hypertension
Junctophilin-2 失调导致肺动脉高压右心室功能障碍的机制
- 批准号:
10436188 - 财政年份:2018
- 资助金额:
$ 67.54万 - 项目类别:
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