Innate Immune Mediated Changes in Renal Function to Cause Hypertension in Females with Autoimmune Disease
先天免疫介导的肾功能变化导致患有自身免疫性疾病的女性高血压
基本信息
- 批准号:10714533
- 负责人:
- 金额:$ 33.23万
- 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:2023-09-01 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAntibody titer measurementAntigensAntioxidantsAttenuatedAutoantibodiesAutoimmuneAutoimmune DiseasesAutoimmunityAutomobile DrivingAwarenessBlood PressureBlood VesselsC-reactive proteinCardiovascular DiseasesCell surfaceCellsCellular StressChronicClinicalClinical DataClinical MarkersComplementDataDatabasesDevelopmentDiseaseErythrocyte Sedimentation RateEssential HypertensionExhibitsFemaleGenerationsGeneticGenetic ModelsHMGB1 geneHeat shock proteinsHumanHypertensionImmuneImmune systemImmunoglobulinsImmunologicsImmunosuppressionImmunotherapyImpairmentInflammasomeInflammationInformaticsInfrastructureInnate Immune ResponseKidneyKidney DiseasesLaboratoriesLigandsLinkLiteratureLow PrevalenceLupusLymphocyteMeasuresMediatingMethodsMitochondriaModelingMusNatural ImmunityObesityOxidative StressPathogenicityPathway interactionsPharmacotherapyPhysiologicalPopulationPrevalenceProductionPublishingReactive Oxygen SpeciesRenal functionRheumatismRheumatoid FactorRiskRoleRuralSerumSignal TransductionSodiumSourceSystemic Lupus ErythematosusTLR4 geneTestingTissuesTubular formationUnited States Department of Veterans AffairsUric AcidWomanabsorptioncardiovascular risk factorcell typeclinical data repositorycohortextracellularhuman modelimprovedin vivoinflammatory markerinnovationinsightkidney vascular structuremenmitochondrial dysfunctionmortalitymouse modelneutrophilnovelpharmacologicyoung woman
项目摘要
Primary hypertension is linked with immunological changes, including autoantibody production, that are
consistent with autoimmune underpinnings of hypertension. The innate immune response also has a central role
in the development of autoimmunity; however, the mechanistic contributions of innate immunity to autoimmune
associated hypertension have not been studied. This proposal will examine a novel innate immune feedforward
mechanism that promotes hypertension during systemic lupus erythematosus (SLE), a disorder that
predominantly affects young women, thus significantly advancing the field towards a better understand of
immune mediated hypertension. We previously showed that an experimental female mouse model of human
SLE exhibits impaired renal vascular function and sodium handling, renal oxidative stress, and hypertension that
is ameliorated by antioxidants. Despite this, little is understood about the cellular sources of reactive oxygen
species or the intracellular pathways that drive changes in renal function during SLE associated hypertension.
The innate immune response has an important role in causing tissue damage during SLE. This proposal will
test the central hypothesis that during SLE there is a feedforward mechanism driving the generation of renal
ROS, leading to impaired renal vascular function and increased tubular sodium reabsorption. This cycle involves
the presence of NETs that increase cell stress signals, including HMGB1, TLR4 mediated mitochondrial
dysfunction, and the production of ROS. Mitochondrial ROS activate the NLRP3 inflammasome, which
perpetuates the cycle by promoting further generation of NETs to induce additional cell stress. This will be tested
in three aims (1) During SLE, NETs promote hypertension by increasing renal ROS that causes impaired renal
vascular and tubular function. (2) During SLE, cell stress proteins (HMGB1) increase mitochondrial ROS
generation leading to NLRP3 inflammasome activation and further NET production through a TLR4 mediated
mechanism. (3) A large data cohort (approximately 32,000) from men and women with SLE will be examined for
relationships between clinical markers of inflammation, immunotherapies, and blood pressure. The proposal
uses widely established models of SLE, an innovative genetic model, state-of-the-art physiological,
pharmacological, and immunological methods, along with a national data base of human clinical data to
rigorously test these aims.
原发性高血压与免疫变化有关,包括自身抗体的产生
项目成果
期刊论文数量(0)
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MICHAEL RYAN其他文献
MICHAEL RYAN的其他文献
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{{ truncateString('MICHAEL RYAN', 18)}}的其他基金
Renal mechanisms of hypertension in autoimmune disease
自身免疫性疾病中高血压的肾脏机制
- 批准号:
9339569 - 财政年份:2015
- 资助金额:
$ 33.23万 - 项目类别:
Renal mechanisms of hypertension in autoimmune disease
自身免疫性疾病中高血压的肾脏机制
- 批准号:
10436800 - 财政年份:2015
- 资助金额:
$ 33.23万 - 项目类别:
Renal mechanisms of hypertension in autoimmune disease
自身免疫性疾病中高血压的肾脏机制
- 批准号:
9113934 - 财政年份:2015
- 资助金额:
$ 33.23万 - 项目类别:
Mississippi Diversity in Hypertension and Cardiorenal Researchers Program
密西西比州高血压和心肾研究人员多样性计划
- 批准号:
8616569 - 财政年份:2014
- 资助金额:
$ 33.23万 - 项目类别:
Mississippi Diversity in Hypertension and Cardiorenal Researchers Program
密西西比州高血压和心肾研究人员多样性计划
- 批准号:
8829330 - 财政年份:2014
- 资助金额:
$ 33.23万 - 项目类别:
Blood Pressure, Renal Hemodynamics, and Inflammation
血压、肾脏血流动力学和炎症
- 批准号:
7834567 - 财政年份:2009
- 资助金额:
$ 33.23万 - 项目类别:
Blood Pressure, Renal Hemodynamics, and Inflammation
血压、肾脏血流动力学和炎症
- 批准号:
7449931 - 财政年份:2008
- 资助金额:
$ 33.23万 - 项目类别:
Blood Pressure, Renal Hemodynamics, and Inflammation
血压、肾脏血流动力学和炎症
- 批准号:
8051642 - 财政年份:2008
- 资助金额:
$ 33.23万 - 项目类别:
Blood Pressure, Renal Hemodynamics, and Inflammation
血压、肾脏血流动力学和炎症
- 批准号:
7800439 - 财政年份:2008
- 资助金额:
$ 33.23万 - 项目类别:
Blood Pressure, Renal Hemodynamics, and Inflammation
血压、肾脏血流动力学和炎症
- 批准号:
7624984 - 财政年份:2008
- 资助金额:
$ 33.23万 - 项目类别:
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Establishment of antibody titer measurement against Vibrio vulnificus
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- 批准号:
19592091 - 财政年份:2007
- 资助金额:
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Grant-in-Aid for Scientific Research (C)














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