Immunophenotyping of Human Hypertension Using Single Cell Multiplex Mass Cytometry to Identify Novel Therapeutic Targets
使用单细胞多重质谱流式细胞仪对人类高血压进行免疫表型分析,以确定新的治疗靶点
基本信息
- 批准号:10000699
- 负责人:
- 金额:$ 47.1万
- 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:2021-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAgeAgingAnimalsAntibodiesB-LymphocytesBlood PressureBody mass indexCellsChronicCytometryDialysis procedureDiseaseExhibitsFunctional disorderGoalsHeartHeart failureHumanHypertensionImmuneImmune systemImmunologicsImmunophenotypingImmunosuppressionIndividualInflammationInflammatoryIsotopesKidney DiseasesKidney FailureLeadMediatingMorbidity - disease rateMusMyocardial InfarctionObesityOrganPeripheral Vascular DiseasesPopulationProductionPublic HealthRare Earth MetalsResidual stateRiskRodentSorting - Cell MovementStimulusStrokeT cell receptor repertoire sequencingT-LymphocyteTherapeuticTimeWidespread Diseasecardiovascular risk factorcytokinedeep sequencingextracellularglobal healthmacrophagemass spectrometermonocytemortalitynew therapeutic targetnormotensivenovelnovel diagnosticsnovel strategiesperipheral bloodprognosticresponsestudy populationtranscriptome sequencing
项目摘要
PROJECT SUMMARY
Hypertension is a major global health concern. In the U.S. alone, one-third of all adults have hypertension and
this rises to two-thirds by the age of 60. Hypertension is a key contributor to morbidity and mortality from
stroke, myocardial infarction, heart failure, peripheral vascular disease, and renal failure/dialysis. Unfortunately,
despite current treatment, blood pressure remains poorly controlled in approximately 50% of individuals with
this disease. Even when blood pressure is reasonably controlled, hypertension is associated with increased
cardiovascular risk. There is emerging evidence from our lab and others that this residual risk and the end-
organ effects of hypertension are largely mediated by inflammation. For example, mice that are deficient in T
cells, B cells, monocytes/macrophages, or one of a number of pro-inflammatory cytokines exhibit blunted
hypertension and reduced end-organ dysfunction in response to hypertensive stimuli. Yet most of these
studies have been conducted in experimental animals, particularly rodents, with limited studies examining the
effect of inflammation in human hypertension. Moreover, global or even partial immunosuppression in humans
is not without risk. To address this problem, the first goal of this proposal is to utilize a cutting-edge single cell
multiplex mass cytometry time of flight (CyTOF) approach to profile the immune cells in the peripheral blood of
normotensive and hypertensive humans to identify unique and possibly rare subpopulations that are altered in
human hypertension. In mass cytometry, antibodies to extracellular and intracellular targets are conjugated to
rare earth metal isotopes that are detected by a mass spectrometer. As obesity and aging are intricately
associated with hypertension, our study population will include people with a range of body mass indices and
age (35 to 75) to determine the extent to which observed hypertensive changes in immune profiles correlate
with obesity and aging. The second goal is to isolate these novel or altered cell populations through flow
sorting and further characterize them by RNA-sequencing, cytokine production, and/or deep sequencing of T
cell receptors in the case of T lymphocytes. Mapping the immunological landscape of hypertension, obesity,
and aging promises to lead to new diagnostic, prognostic, and therapeutic strategies to treat human
hypertension and limit the associated end-organ damage from this chronic, widespread disease without
inducing global immunosuppression.
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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Meenakshi Swaminathan Madhur其他文献
Meenakshi Swaminathan Madhur的其他文献
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{{ truncateString('Meenakshi Swaminathan Madhur', 18)}}的其他基金
Diverse Roles of Interleukin 17 Isoforms in the Pathogenesis of Hypertension
白细胞介素 17 亚型在高血压发病机制中的多种作用
- 批准号:
8617022 - 财政年份:2014
- 资助金额:
$ 47.1万 - 项目类别:
Diverse Roles of Interleukin 17 Isoforms in the Pathogenesis of Hypertension
白细胞介素 17 亚型在高血压发病机制中的多种作用
- 批准号:
9205258 - 财政年份:2014
- 资助金额:
$ 47.1万 - 项目类别:
Diverse Roles of Interleukin 17 Isoforms in the Pathogenesis of Hypertension
白细胞介素 17 亚型在高血压发病机制中的多种作用
- 批准号:
9275079 - 财政年份:2014
- 资助金额:
$ 47.1万 - 项目类别:
Role of T Cell and Vascular NADPH Oxidases in Angiotensin II Induced Hypertension
T 细胞和血管 NADPH 氧化酶在血管紧张素 II 诱导的高血压中的作用
- 批准号:
7486017 - 财政年份:2008
- 资助金额:
$ 47.1万 - 项目类别:
Role of T Cell and Vascular NADPH Oxidases in Angiotensin II Induced Hypertension
T 细胞和血管 NADPH 氧化酶在血管紧张素 II 诱导的高血压中的作用
- 批准号:
7693802 - 财政年份:2008
- 资助金额:
$ 47.1万 - 项目类别:
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