Formyl peptide receptor activation induces vascular plasticity and remodeling inhypertension
甲酰基肽受体激活诱导高血压血管可塑性和重塑
基本信息
- 批准号:10460675
- 负责人:
- 金额:$ 36万
- 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:2021-01-15 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:ActinsAdvanced DevelopmentAffectAnimalsArteriesAttentionBacteriaBindingBloodBlood CirculationBlood PressureBlood VesselsCell DeathCellsCharacteristicsDataEnzymesFPR1 geneFunctional disorderG-Protein-Coupled ReceptorsGTP-Binding Protein alpha Subunits, GsGenetic EngineeringGerm-FreeGoalsHumanHypertensionImmuneImmune systemImmunobiologyInflammationInfusion proceduresInnate Immune SystemInstitutional Review BoardsInterdisciplinary StudyIntrinsic factorLeadLeaky GutLegal patentLeukocytesLinkLipopolysaccharidesLiteratureMeasuresMediatingMitochondriaModelingMolecularMovementNational Heart, Lung, and Blood InstitutePatientsPattern recognition receptorPeptidesPlayRattusReceptor ActivationResearchResearch PersonnelResearch Project GrantsRoleSentinelSignal PathwaySourceTechnologyTestingTherapeuticTimeTranslational ResearchVascular DiseasesVascular remodelingarterial remodelingbasecell injurycell motilitydriving forcefMet-Leu-Phe receptorformyl peptidegut microbiotainnate immune functioninnovationmicrobiotanetwork dysfunctionneutrophilnormotensivenovelnovel therapeutic interventionpathogenpolymerizationpressurepreventreceptorsensortranslational studyvascular injury
项目摘要
Project Summary WENCESLAU, CAMILLA F.
One of the major pathophysiological characteristics of hypertension is the presence of vascular
remodeling. Accordingly, it has been shown that 100% hypertensive subjects present small artery remodeling.
However, there is a gap in the literature in understanding the exact trigger that leads to vascular remodeling, and
this may limit our ability to adequately treat and prevent hypertension.
Recent evidence implicates immune mechanisms in the pathophysiology of hypertension. Formyl peptide
receptor (FPR) -1 is a pattern recognition receptor which plays a crucial role in the function of the innate immune
system. In fact, one of the most powerful signaling pathways that induces actin polymerization and neutrophil
movement is mediated by FPR-1. Recently, we observed that this receptor is expressed in arteries. Therefore,
we questioned why a receptor that is crucial for immune defense and cell motility in leukocytes, would be
expressed and functional in arteries? We observed that activation of FPR-1 in arteries is important for the
temporal reorganization of actin, which rapidly induces actin polymerization.
FPR-1 is a G-protein-coupled receptor that can bind N-formyl peptides produced by bacterial
degradation. Interestingly, mitochondria carry hallmarks of their bacterial ancestry. Consequently, both
mitochondrial and bacterial-derived peptides have a formyl group at their N-terminus. Therefore, N-formyl
peptides (NFPs), regardless of origin, are recognized by FPR-1 as pathogens and thus play a role in the initiation
of inflammation. Here, we observed for the first time that NFPs are present in the circulation of hypertensive
animals. Therefore, it is plausible to suggest that synergistic action of leaky gut-derived bacteria NFPs and cell
damage-derived mitochondria NFPs lead to FPR-1 activation. Consequently, FPR-1 activation maybe the trigger
to induce vascular remodeling, via actin polymerization, and subsequently, hypertension.
This planned research is uniquely suited to the NHLBI Early Stage Investigator (ESI)-Research Project
Grant, because it is unique, innovative and it has a strong, translational and multi-disciplinary research team of
collaborators that have the capabilities and expertise to make this project successful. As an independent ESI,
my short-term goal is to use state-of-art approaches, including culture-pressure myographs, genetic-
engineering technologies, and arteries from humans and animals to explore a major driving force behind
vascular-immune network dysfunction in hypertension.
项目概述:
项目成果
期刊论文数量(0)
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Camilla Ferreira Wenceslau其他文献
Camilla Ferreira Wenceslau的其他文献
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{{ truncateString('Camilla Ferreira Wenceslau', 18)}}的其他基金
Formyl peptide receptor activation induces vascular plasticity and remodeling inhypertension
甲酰基肽受体激活诱导高血压血管可塑性和重塑
- 批准号:
10328974 - 财政年份:2021
- 资助金额:
$ 36万 - 项目类别:
Formyl peptide receptor activation induces vascular plasticity and remodeling in hypertension
甲酰基肽受体激活诱导高血压血管可塑性和重塑
- 批准号:
10112987 - 财政年份:2021
- 资助金额:
$ 36万 - 项目类别:
Formyl peptide receptor activation induces vascular plasticity and remodeling inhypertension
甲酰基肽受体激活诱导高血压血管可塑性和重塑
- 批准号:
10544019 - 财政年份:2021
- 资助金额:
$ 36万 - 项目类别:
Intrarenal Arteries Sense N-formyl Peptides Leading to Vascular Injury in Sepsis
肾内动脉感知 N-甲酰肽导致脓毒症血管损伤
- 批准号:
9883818 - 财政年份:2016
- 资助金额:
$ 36万 - 项目类别:
Intrarenal Arteries Sense N-formyl Peptides Leading to Vascular Injury in Sepsis
肾内动脉感知 N-甲酰肽导致脓毒症血管损伤
- 批准号:
10058843 - 财政年份:2016
- 资助金额:
$ 36万 - 项目类别:
Intrarenal Arteries Sense N-formyl Peptides Leading to Vascular Injury in Sepsis
肾内动脉感知 N-甲酰肽导致脓毒症血管损伤
- 批准号:
10450907 - 财政年份:2016
- 资助金额:
$ 36万 - 项目类别:
Intrarenal Arteries Sense Trauma-derived Mitochondrial N-formyl Peptides Leading to Kidney Injury in SIRS
肾内动脉感知创伤源性线粒体 N-甲酰肽导致 SIRS 肾损伤
- 批准号:
9333390 - 财政年份:2016
- 资助金额:
$ 36万 - 项目类别:
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