Role of JNK and BNP in Septic Hypotension

JNK 和 BNP 在脓毒性低血压中的作用

基本信息

  • 批准号:
    10265517
  • 负责人:
  • 金额:
    $ 36.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-20 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

Modified Project Summary/Abstract Section Sepsis is the body’s overwhelming immune response to infection that leads to organ failure and death. Refractory hypotension despite administration of vasopressors and fluid resuscitation is the most severe consequence of sepsis with a ~50% in-hospital mortality rate. Currently, there are no targeted therapies to treat sepsis. Existing treatment guidelines focus on source control and supportive care, including early administration of antibiotics and fluid resuscitation. Thus, novel genes and pathways that are involved in the pathophysiology of sepsis are actively sought with the goal to identify new targets that may offer novel therapeutic approaches. Cardiac dysfunction and hypotension in sepsis are associated with poor prognosis and increased mortality. Elevated circulating levels of B-type natriuretic peptide (BNP) correlate with myocardial stress in sepsis, as well as in other types of heart failure. Our data identified a signaling pathway that increased BNP production leads to lower cardiac output. Our previous studies and new data show that cardiac JNK activation, which we have shown to be involved in sepsis pathophysiology, increases BNP expression in septic mice. Our new data show that JNK inhibition increases blood pressure and tissue perfusion in septic mice and this is associated with lower plasma BNP levels. Thus, our central hypothesis is that inhibition of circulating BNP will alleviate septic hypotension and improve survival. To address our hypothesis we have designed the following specific aim: Aim 1 - To assess the role of BNP in reducing CO and promoting hypotension in septic mice and patients. In summary, our goal is to elucidate the role of BNP in the pathophysiology of septic hypotension and explore the therapeutic potential of treatment strategies aimed at regulating BNP expression or neutralizing circulating BNP. Simultaneously, we will pursue clinical studies to evaluate the translational impact of our findings. Thus, we anticipate our findings to constitute the basis for designing future clinical applications aiming to alleviate septic hypotension and organ hypo-perfusion.
修改项目摘要/摘要部分 脓毒症是身体对感染的压倒性免疫反应,导致器官衰竭和死亡。尽管给予血管加压药和液体复苏,顽固性低血压是脓毒症最严重的后果,院内死亡率约为50%。目前,没有靶向疗法来治疗脓毒症。现有的治疗指南侧重于源头控制和支持性护理,包括早期使用抗生素和液体复苏。因此,积极寻找参与脓毒症病理生理学的新基因和途径,目的是鉴定可提供新治疗方法的新靶点。脓毒症患者的心功能不全和低血压与预后不良和死亡率增加有关。B型利钠肽(BNP)循环水平升高与脓毒症以及其他类型心力衰竭的心肌应激相关。我们的数据确定了一个信号通路,增加BNP产生导致心输出量降低。我们以前的研究和新的数据表明,心脏JNK激活,我们已经表明,参与脓毒症的病理生理,增加脑钠肽的表达在脓毒症小鼠。我们的新数据表明,JNK抑制增加脓毒症小鼠的血压和组织灌注,这与较低的血浆BNP水平有关。因此,我们的中心假设是,抑制循环BNP将减轻感染性低血压,提高生存率。为了解决我们的假设,我们设计了以下具体目标:目标1 -评估BNP在脓毒症小鼠和患者中降低CO和促进低血压的作用。总之,我们的目标是阐明BNP在感染性低血压的病理生理学中的作用,并探索旨在调节BNP表达或中和循环BNP的治疗策略的治疗潜力。同时,我们将进行临床研究,以评估我们的研究结果的转化影响。因此,我们期望我们的研究结果构成设计未来临床应用的基础,旨在减轻感染性低血压和器官灌注不足。

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 }}

Konstantinos Drosatos其他文献

Konstantinos Drosatos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('Konstantinos Drosatos', 18)}}的其他基金

Role of cardiomyocyte KLF5 in heart failure
心肌细胞KLF5在心力衰竭中的作用
  • 批准号:
    10666690
  • 财政年份:
    2022
  • 资助金额:
    $ 36.58万
  • 项目类别:
Role of cardiomyocyte KLF5 in heart failure
心肌细胞KLF5在心力衰竭中的作用
  • 批准号:
    10591922
  • 财政年份:
    2022
  • 资助金额:
    $ 36.58万
  • 项目类别:
Role of JNK and BNP in Septic Hypotension
JNK 和 BNP 在脓毒性低血压中的作用
  • 批准号:
    10389857
  • 财政年份:
    2020
  • 资助金额:
    $ 36.58万
  • 项目类别:
Role of KLF5 in cardiac and systemic fatty acid metabolism
KLF5 在心脏和全身脂肪酸代谢中的作用
  • 批准号:
    9919371
  • 财政年份:
    2016
  • 资助金额:
    $ 36.58万
  • 项目类别:
Role of KLF5 in cardiac and systemic fatty acid metabolism
KLF5 在心脏和全身脂肪酸代谢中的作用
  • 批准号:
    9006831
  • 财政年份:
    2016
  • 资助金额:
    $ 36.58万
  • 项目类别:
Mechanisms of Reduced Fatty Acid Oxidation and Cardiac Dysfunction in Sepsis
脓毒症中脂肪酸氧化减少和心脏功能障碍的机制
  • 批准号:
    8470701
  • 财政年份:
    2012
  • 资助金额:
    $ 36.58万
  • 项目类别:
Mechanisms of Reduced Fatty Acid Oxidation and Cardiac Dysfunction in Sepsis
脓毒症中脂肪酸氧化减少和心脏功能障碍的机制
  • 批准号:
    8828402
  • 财政年份:
    2012
  • 资助金额:
    $ 36.58万
  • 项目类别:
Mechanisms of Reduced Fatty Acid Oxidation and Cardiac Dysfunction in Sepsis
脓毒症中脂肪酸氧化减少和心脏功能障碍的机制
  • 批准号:
    9088504
  • 财政年份:
    2012
  • 资助金额:
    $ 36.58万
  • 项目类别:
Mechanisms of Reduced Fatty Acid Oxidation and Cardiac Dysfunction in Sepsis
脓毒症中脂肪酸氧化减少和心脏功能障碍的机制
  • 批准号:
    8278334
  • 财政年份:
    2012
  • 资助金额:
    $ 36.58万
  • 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:
    $ 36.58万
  • 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:
    $ 36.58万
  • 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:
    $ 36.58万
  • 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:
    $ 36.58万
  • 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:
    $ 36.58万
  • 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:
    $ 36.58万
  • 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:
    $ 36.58万
  • 项目类别:
    EU-Funded
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:
    $ 36.58万
  • 项目类别:
    Standard Grant
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:
    $ 36.58万
  • 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:
    $ 36.58万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了