Transcriptomics, pathobiology, and cardiac event in hypertrophic cardiomyopathy
肥厚型心肌病的转录组学、病理学和心脏事件
基本信息
- 批准号:10638722
- 负责人:
- 金额:$ 75.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAgeAnimalsArrhythmiaBiologicalBiological MarkersCardiacCardiomyopathiesCardiovascular systemClinicalClinical DataClinical ManagementClinical MarkersDataDevelopmentDevicesDiseaseDisease ProgressionEnrollmentEventFamilyGene MutationGeneticGoalsHeartHeart DiseasesHeart HypertrophyHeart failureHeterogeneityHumanHypertrophic CardiomyopathyImageIn Situ HybridizationInterventionInterviewKnowledgeLeftLeft Ventricular HypertrophyMAP Kinase GeneMatched Case-Control StudyMediatingMedical RecordsMessenger RNAMicroRNAsModelingMolecularMolecular TargetMyocardial dysfunctionMyocardiumNational Heart, Lung, and Blood InstitutePathogenesisPathway interactionsPatient SelectionPatientsPersonsPharmacotherapyPhenotypePlasmaPreventive therapyProspective StudiesProspective cohortProteomicsQuantitative Reverse Transcriptase PCRRNARecording of previous eventsReportingResearchResearch PersonnelRiskRoleSamplingSignal PathwaySpecific qualifier valueStrategic PlanningStrokeSystemTestingTimeTranscriptUntranslated RNAUp-RegulationValidationVentricularWorkbiobankcirculating microRNAclinical heterogeneityclinical phenotypecohortdisorder preventiondrug developmentevidence baseexperiencefollow-uphigh riskhypertensiveimplantationimprovedinhibitorinsightmicroRNA biomarkersmolecular drug targetnovelnovel strategiespreventpreventive interventionprospectiveresponseretention raterisk stratificationsexsudden cardiac deathtargeted treatmenttranscriptome sequencingtranscriptomic profilingtranscriptomics
项目摘要
PROJECT SUMMARY
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease and causes
major adverse cardiovascular events (MACE) – e.g., arrhythmias, heart failure, and sudden
cardiac death. Invasive interventions to prevent MACE are available but can result in
complications. Current risk stratification strategy has limited power to predict which patient
would develop MACE and benefit most from preventive interventions. Furthermore, little is
known about the signaling pathways through which gene mutations mediate HCM pathobiology
and MACE. These major knowledge gaps have hindered efforts to prevent MACE in HCM. The
Harvard-Columbia Multi-center Hypertrophic Cardiomyopathy (HCM2) Biorepository is an
ongoing 3-center prospective cohort that enrolled 615 patients with HCM during 2014-2022. In
this large multi-center HCM biorepository, investigators have collected high-quality
biospecimens – i.e., 615 plasma and 120 left ventricular myocardium. Follow-up data include
biannual interviews, medical record reviews, and in-person exam every year, with >85% follow-
up to date (median follow-up, 3.1 years). The present R01 project will extend this large well-
characterized HCM biorepository by transcriptomically profiling both myocardium and plasma
samples in parallel, and by examining their relations to both HCM disease status and MACE. In
Aim 1, we will examine the association of signaling pathway dysregulation in the myocardium
with HCM disease status using qRT-PCR, single-transcript RNA-FISH, and RNA-Seq. In Aim 2,
we will specify signaling pathways and plasma circulating microRNAs that predict new-onset
MACE using transcriptomic profiling. Finally, using an unsupervised clustering-based approach,
Aim 3 will define HCM subtypes by integrating genetic, transcriptomic, proteomic, and clinical
data, and determine their associations with MACE. Our prior studies and preliminary work lend
compelling support to our hypotheses. The present R01 project will provide a unique opportunity
to reveal the molecular mechanisms of HCM pathobiology and progression to MACE through
examining signaling pathways by applying transcriptomic profiling to paired myocardium and
plasma. Moreover, the proposed study will also derive a novel risk stratification system in HCM,
which will allow us to precisely identify high-risk HCM subtypes that would benefit from
preventive interventions. The project will provide a strong evidence base for developing targeted
pharmacotherapies to prevent HCM pathogenesis and MACE through the modulation of specific
signaling pathways. The investigators have complementary and integrated expertise in all
relevant fields. The study matches well with the NHLBI strategic plan for HCM research.
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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Yuichi Shimada其他文献
Yuichi Shimada的其他文献
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{{ truncateString('Yuichi Shimada', 18)}}的其他基金
Proteomics profiling in hypertrophic cardiomyopathy and cardiac event prediction
肥厚型心肌病和心脏事件预测的蛋白质组学分析
- 批准号:
10184112 - 财政年份:2021
- 资助金额:
$ 75.75万 - 项目类别:
Proteomics profiling in hypertrophic cardiomyopathy and cardiac event prediction
肥厚型心肌病和心脏事件预测的蛋白质组学分析
- 批准号:
10372158 - 财政年份:2021
- 资助金额:
$ 75.75万 - 项目类别:
Proteomics profiling in hypertrophic cardiomyopathy and cardiac event prediction
肥厚型心肌病和心脏事件预测的蛋白质组学分析
- 批准号:
10600983 - 财政年份:2021
- 资助金额:
$ 75.75万 - 项目类别:
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