Mosaic loss of Y chromosome in blood and heart failure
血液中 Y 染色体马赛克丢失与心力衰竭
基本信息
- 批准号:10277645
- 负责人:
- 金额:$ 43.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-15 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAddressAgeAgingBiological AgingBiological MarkersBloodBlood CellsCRISPR/Cas technologyCardiacCardiometabolic DiseaseCardiovascular DiseasesCoculture TechniquesCodeDNA Sequence AlterationDataDiseaseElderlyExhibitsFibroblastsFrequenciesGenesGenomic InstabilityHeartHeart failureHematologic NeoplasmsHematopoiesisHematopoietic NeoplasmsHistologicHumanHypertrophyInflammationKnockout MiceKnowledgeLightLinkLongevityModelingMosaicismMusMutateMutationMyocardialMyocardiumPathologicPathologyPhenotypePrecancerous ConditionsProceduresProcessProteinsRecurrenceResearchRiskRoleSex DifferencesSignal TransductionTestingTherapeuticTransforming Growth Factor betaWomanWorkY Chromosomeage relatedbasecardioprotectioncardiovascular risk factorchromosome Y lossconstrictioncoronary fibrosisepidemiology studyinterestmacrophagemalemenmortalitymouse modelnovelpremalignantpressuretargeted treatment
项目摘要
SUMMARY
Recent technological advances indicate that somatic DNA mutations accumulate with age and are remarkably
prevalent. The accumulation of mutations in blood cells has been associated with increases in all-cause
mortality and cardiometabolic diseases. Studies have focused on the precancerous clonal hematopoiesis state
that results from mutations in “driver” genes that recurrently mutate in blood cancers. However, this class of
mutations represent a small fraction of the total somatic mosaicism that occurs in blood. Mosaic loss of the Y
chromosome (mLoY) in blood is the most common post-zygotic mutation in humans. Epidemiological studies
have associated mLoY with all-cause mortality and a number of age-associated diseases. However, it is
unknown whether there is a causal connection between mLoY and cardiovascular disease. Here, we will
employ multiple murine models to assess the impact of mLoY in heart failure, and investigate this relationship
at a mechanistic level.
总结
最近的技术进展表明,体细胞DNA突变随着年龄的增长而积累,
普遍存在。血细胞中突变的积累与各种原因的增加有关。
死亡率和心脏代谢疾病。研究主要集中在癌前克隆性造血状态
这是由在血癌中反复突变的“驱动”基因突变引起的。然而,这一类
突变代表了血液中发生的总体细胞嵌合现象的一小部分。Y染色体的镶嵌丢失
血液中的mLoY是人类最常见的合子后突变。流行病学研究
mLoY与全因死亡率和许多年龄相关疾病相关。但据
尚不清楚mLoY与心血管疾病之间是否存在因果关系。在这里,我们将
采用多种鼠模型评估mLoY对心力衰竭的影响,并研究这种关系
在机械的层面上。
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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KENNETH WALSH其他文献
KENNETH WALSH的其他文献
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{{ truncateString('KENNETH WALSH', 18)}}的其他基金
Clonal hematopoiesis and severity of COVID-19 disease
克隆造血和 COVID-19 疾病的严重程度
- 批准号:
10196497 - 财政年份:2021
- 资助金额:
$ 43.06万 - 项目类别:
Clonal hematopoiesis and severity of COVID-19 disease
克隆造血和 COVID-19 疾病的严重程度
- 批准号:
10413986 - 财政年份:2021
- 资助金额:
$ 43.06万 - 项目类别:
Mosaic loss of Y chromosome in blood and heart failure
血液中 Y 染色体马赛克丢失与心力衰竭
- 批准号:
10714372 - 财政年份:2021
- 资助金额:
$ 43.06万 - 项目类别:
Mosaic loss of Y chromosome in blood and heart failure
血液中 Y 染色体马赛克丢失与心力衰竭
- 批准号:
10646348 - 财政年份:2021
- 资助金额:
$ 43.06万 - 项目类别:
Role of therapy-related clonal hematopoiesis in anthracycline-induced cardiotoxicity
治疗相关克隆造血在蒽环类药物引起的心脏毒性中的作用
- 批准号:
10394732 - 财政年份:2020
- 资助金额:
$ 43.06万 - 项目类别:
Role of therapy-related clonal hematopoiesis in anthracycline-induced cardiotoxicity
治疗相关克隆造血在蒽环类药物引起的心脏毒性中的作用
- 批准号:
10172973 - 财政年份:2020
- 资助金额:
$ 43.06万 - 项目类别:
Role of therapy-related clonal hematopoiesis in anthracycline-induced cardiotoxicity
治疗相关克隆造血在蒽环类药物引起的心脏毒性中的作用
- 批准号:
10614493 - 财政年份:2020
- 资助金额:
$ 43.06万 - 项目类别:
Hematopoietic stem cell mutations and ischemic cardio-metabolic disease
造血干细胞突变与缺血性心脏代谢疾病
- 批准号:
9900053 - 财政年份:2019
- 资助金额:
$ 43.06万 - 项目类别:
Hematopoietic stem cell mutations and ischemic cardio-metabolic disease
造血干细胞突变与缺血性心脏代谢疾病
- 批准号:
10378063 - 财政年份:2019
- 资助金额:
$ 43.06万 - 项目类别:
Clonal hematopoiesis and accelerated metabolic dysfunction in obesity
肥胖症中的克隆造血和加速代谢功能障碍
- 批准号:
10390471 - 财政年份:2019
- 资助金额:
$ 43.06万 - 项目类别:
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