Cardiac fibroblast inflammasome and atrial myopathy
心脏成纤维细胞炎症小体与心房肌病
基本信息
- 批准号:10597243
- 负责人:
- 金额:$ 69.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-25 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:Action PotentialsAddressAffectAnti-Inflammatory AgentsAreaArrhythmiaAtrial FibrillationAttenuatedAutomobile DrivingCardiacCardiac MyocytesCellsChronicComplexContractile ProteinsCouplingDataDevelopmentEvaluationEvolutionExhibitsFamilyFibroblastsFibrosisFunctional disorderGenetic TranscriptionGlucocorticoid ReceptorHCN4 geneHeart AtriumHistologyImpairmentInfarctionInflammasomeInflammationInflammatoryInflammatory ResponseInterleukinsKnock-in MouseLeftLeft atrial structureMacrophageMaintenanceMapsMediatingMessenger RNAModelingMolecularMorbidity - disease rateMusMyocardiumMyopathyNCOA3 geneNuclearOpticsOutcome StudyPacemakersPathogenesisPathologyPathway interactionsPatientsPeroxisome Proliferator-Activated ReceptorsPhasePhenocopyPhenotypePilot ProjectsPredispositionPrevalencePreventionProfibrotic signalProteinsPublic HealthRecombinant InterleukinsResolutionRoleSignal TransductionSinoatrial NodeSinusTestingTherapeuticWorkcombatefficacy evaluationheart functionimaging studyimprovedinsightknock-downmarenostrinmortalityneutralizing antibodynovelparacrinepatch clamppreventresponsetranscription factor
项目摘要
PROJECT SUMMARY
Atrial fibrillation (AF) is the most frequent arrhythmia. Atrial myopathy is a key determinant of the development
of AF. The molecular mechanisms underlying the evolution of AF-promoting atrial myopathy are complex and
poorly understood. Innate inflammatory signaling including the ‘NLR family pyrin domain containing 3’ (NLRP3)
inflammasome pathway can modulate cardiac function and atrial arrhythmogenesis. Our preliminary study
revealed that NLRP3 inflammasome activity is enhanced in atrial cardiac fibroblasts (CFs) of persistent AF
patients compared with sinus rhythm controls. The CF-specific activation of NLRP3 in mice promotes the
development of atrial fibrosis, enlarged left atrium, reduced atrial contractility, abnormal impulse conduction,
sinus node dysfunction, and increased AF susceptibility, phenocopying atrial myopathy associated with AF
development. In this proposal, we will test the hypothesis that activation of CF inflammasomes enhances atrial
arrhythmogenesis by promoting atrial myopathy. Additionally, the therapeutic potential of enhancing the
resolution of inflammation to combat atrial myopathy and atrial arrhythmogenesis deserves evaluation. In this
proposal, we will also evaluate whether an inducer of inflammation resolution can prevent the inflammasome-
induced atrial myopathy, thereby reducing atrial arrhythmogenesis. This proposal addresses several
understudied areas in AF pathogenesis. The outcome of this study will provide novel insights into the
development of atrial myopathy and sinus node dysfunction, as well as provide rationale for using the pro-
resolution molecule in AF prevention.
项目总结
房颤是最常见的心律失常。房性肌病是发展的关键决定因素。
自动对讲机。房颤促进性心房肌病演变的分子机制是复杂的和
人们对此知之甚少。包括‘NLR家族3’(NLRP3)在内的先天炎症信号
炎性小体途径可调节心功能和房性心律失常的发生。我们的初步研究
持续性房颤患者心房成纤维细胞中NLRP3炎症体活性增强
患者与窦性心律对照组进行比较。NLRP3在小鼠体内的Cf特异性激活促进
出现心房纤维化,左心房增大,心房收缩能力降低,脉冲传导异常,
窦房结功能障碍和房颤易感性增加,与房颤相关的表现性心房肌病
发展。在这个方案中,我们将检验这样一种假设,即激活CF炎性小体可以增强心房功能
促进房性肌病引起的心律失常。此外,加强治疗的潜力
对抗房肌病和房性心律失常的炎症消退值得评价。在这
我们还将评估消炎诱导剂是否可以预防炎症小体-
诱发房性肌病,从而减少房性心律失常的发生。这项提案涉及几个
房颤发病机制研究不足的领域。这项研究的结果将为研究
房性肌病和窦房结功能障碍的发展,以及使用PRO的理论基础。
房颤预防中的分辨分子。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Na Li其他文献
Na Li的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Na Li', 18)}}的其他基金
The Role of Gasdermin-D/Interleukin-1 Nexus in Atrial Arrhythmogenesis
Gasdermin-D/IL-1 Nexus 在房性心律失常发生中的作用
- 批准号:
10531927 - 财政年份:2021
- 资助金额:
$ 69.97万 - 项目类别:
The Role of Gasdermin-D/Interleukin-1 Nexus in Atrial Arrhythmogenesis
Gasdermin-D/IL-1 Nexus 在房性心律失常发生中的作用
- 批准号:
10363449 - 财政年份:2021
- 资助金额:
$ 69.97万 - 项目类别:
The Role of Gasdermin-D/Interleukin-1 Nexus in Atrial Arrhythmogenesis
Gasdermin-D/IL-1 Nexus 在房性心律失常发生中的作用
- 批准号:
10779536 - 财政年份:2021
- 资助金额:
$ 69.97万 - 项目类别:
Mechanisms underlying atrial fibrillation associated with chronic kidney disease
与慢性肾脏病相关的心房颤动的机制
- 批准号:
10376782 - 财政年份:2019
- 资助金额:
$ 69.97万 - 项目类别:
Mechanisms underlying atrial fibrillation associated with chronic kidney disease
与慢性肾脏病相关的心房颤动的机制
- 批准号:
9913385 - 财政年份:2019
- 资助金额:
$ 69.97万 - 项目类别:
Inflammasome mediated pathogenesis of atrial fibrillation
炎症小体介导的房颤发病机制
- 批准号:
9336416 - 财政年份:2016
- 资助金额:
$ 69.97万 - 项目类别:
New Building Blocks for the Synthesis of Modified RNAs
用于合成修饰 RNA 的新构件
- 批准号:
8252504 - 财政年份:2012
- 资助金额:
$ 69.97万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 69.97万 - 项目类别:
Research Grant