Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults
Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults
批准号:
10711393
负责人:
Vasantha Kolavennu Jotwani
金额:
$38.33万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-09-01 至 2025-07-31
关键词:
AccelerationAdultAffectAgeAgingAlzheimer disease preventionAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaBioenergeticsBioinformaticsBloodBlood PressureBody CompositionBrainCessation of lifeClinical DataClinical ResearchClinical TrialsDNADataDefectDementiaDiabetes MellitusDiseaseDisease ProgressionElderlyEnergy MetabolismEpidemiologyEuropean ancestryExperimental ModelsFrontotemporal DementiaFundingFutureGenerationsGenesGeneticGenomeHealthImpaired cognitionIndividualIndividual DifferencesInheritedInterventionIntervention TrialKidney DiseasesKnowledgeLewy Body DementiaLinkMeasurementMeasuresMethodsMitochondriaMitochondrial DNAModelingMutationNational Heart, Lung, and Blood InstituteNerve DegenerationNeurodegenerative DisordersOrganOrganellesOutcomeOxidative PhosphorylationParentsParticipantPathogenesisPersonsPopulation HeterogeneityReactive Oxygen SpeciesResearch PersonnelRiskRisk FactorsRoleSample SizeSomatic MutationSpecimenStressStructureTherapeuticUnited StatesVariantVascular DementiaWorkage relatedagedblood pressure interventionbrain healthbrain tissueburden of illnesscandidate markercardiovascular disorder riskcardiovascular risk factorclinical riskcognitive functioncohortdementia riskeffective therapyepidemiology studyhigh riskhypertensiveimprovedinnovationinterestlifestyle interventionmitochondrial DNA mutationmitochondrial dysfunctionmitochondrial genomemortalitymultidisciplinarynovelresponseresponse biomarkerstudy populationtargeted treatmenttherapy development
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) are increasingly common
neurodegenerative conditions that are fatal and progressive due to the lack of effective treatments.
Mitochondria are intracellular organelles that are essential for energy metabolism and stress adaptation.
Experimental models suggest that mitochondrial dysfunction occurs early in the pathogenesis of AD/ADRD,
and damaged mitochondria have been observed in brain tissue of persons with AD/ADRD. Recent
epidemiologic studies have linked aberrations in mitochondrial DNA (mtDNA) quantity and quality with several
age-related outcomes, including risk of cardiovascular disease, kidney disease, and death, but their
associations with cognitive function and dementia risk are not well-established.
This AD/ADRD supplement will capitalize on an existing parent R01 to investigate the impact of blood-based
measures of mtDNA quantity and quality on brain health among over 16,000 participants of four clinical
studies: the Health, Aging and Body Composition Study (Health ABC, N=3,075); the Lifestyle Interventions and
Independence for Elders Study (LIFE, N=1,755); the Systolic Blood Pressure Intervention Trial (SPRINT,
N=9,361) and the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD, N=2,488). Our first Aim
will determine whether mtDNA quantity, assessed by blood mtDNA copy number, is associated with risk of
cognitive decline and dementia, independent of traditional clinical risk factors. Our second Aim will evaluate
associations of mtDNA quality, assessed by inherited and acquired mtDNA mutations, with risk of cognitive
decline and dementia using an innovative approach for integration of mutation burden across functional
regions of the mitochondrial genome. These projects will: 1) generate novel hypotheses into the relationships
between mitochondrial dysfunction and brain health; 2) advance mtDNA quantity and quality as candidate
biomarkers of response to future interventions for AD/ADRD that promote mitochondrial health; and 3) inform
enrichment of participants for future clinical trials of mitochondria-targeted therapies for treatment or prevention
of AD/ADRD.
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Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults
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批准号:10470375
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项目类别:
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资助金额:$71.44万
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财政年份:2021
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负责人:Vasantha Kolavennu Jotwani
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依托单位:
Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults
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批准号:10210130
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资助金额:$75.78万
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负责人:Vasantha Kolavennu Jotwani
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依托单位:
Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults
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批准号:10679021
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项目类别:
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Cannabis use and kidney health among veterans with coronary artery disease
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批准号:10261058
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财政年份:2020
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依托单位:
Biomarkers of Drug-induced Kidney Injury in HIV
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批准号:9351503
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资助金额:$19.84万
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财政年份:2016
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负责人:Vasantha Kolavennu Jotwani
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依托单位:
Biomarkers of Drug-induced Kidney Injury in HIV
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批准号:9270400
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项目类别:
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资助金额:$19.98万
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财政年份:2016
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负责人:Vasantha Kolavennu Jotwani
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依托单位:
Novel biomarkers of kidney injury in HIV-infected men
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批准号:8958708
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项目类别:
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资助金额:$8.02万
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财政年份:2014
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负责人:Vasantha Kolavennu Jotwani
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依托单位:
Novel biomarkers of kidney injury in HIV-infected men
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批准号:8783329
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项目类别:
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资助金额:$7.7万
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财政年份:2014
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负责人:Vasantha Kolavennu Jotwani
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依托单位:
海外基金