Role of Renal Lymphatics in Blood Pressure Regulation

肾淋巴管在血压调节中的作用

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT Almost 1 in 2 Americans will develop hypertension (HTN) while half of these people will develop salt-sensitive hypertension (SSHTN). Precision medicine and novel therapies that combat the cardiovascular and renal complications of HTN and SSHTN are critically needed. The long-term goal is to develop a safe and effective therapeutic that targets renal lymphatic vessels to reduce renal injury and HTN. The objectives of this application are to determine the role that renal lymphatics play in renal immune cell accumulation and inflammation in HTN and whether increasing renal lymphatics can reduce renal injury and blood pressure. HTN is associated with activated immune cell infiltration into the kidney leading to interstitial inflammation and renal injury. The resolution of inflammation involves an increase in lymphatic vessels to clear the interstitial immune cells and fluid, but inadequate lymphatic responses result in persistent inflammation and tissue injury. Accumulation of pro-inflammatory immune cells in the kidney plays a key role in HTN; however, the role of renal lymphatics in HTN is unknown. The central hypotheses are that (1) HTN stimuli (salt, angiotensin II, asymmetric dimethylarginine) cause immune cell activation, infiltration, and inflammation in the kidney which contributes to a compensatory increase in renal lymphatics, (2) HTN stimuli in the renal interstitial fluid directly affects renal lymphatic cell biology and function, and (3) that further augmenting renal lymphatics is sufficient to attenuate renal injury and HTN. Recent publications and preliminary data support these hypotheses. The hypotheses will be tested by 3 specific aims: (Aim 1) Determine how renal lymphatics are affected in HTN and the mechanisms involved; (Aim 2) Determine how HTN stimuli directly impact lymphatic cell biology and function; and (Aim 3) Determine how inducing renal lymphangiogenesis affects renal inflammation and HTN. Various combinations of pharmacologic and genetic perturbations of renal lymphatics in mice as well as the examination of molecular mechanisms in lymphatic cells and isolated vessels will be used. The study will also examine renal lymphatics in humans with and without HTN as well as develop and test a kidney-specific nanoparticle that induces lymphangiogenesis. The innovation of the proposed research lies in the elucidation of the role that lymphatic vessels in the kidney play in renal inflammation and blood pressure regulation and how augmenting renal lymphatics can reduce kidney injury and HTN. Technical innovation includes the development of unique transgenic mice and a kidney-specific lymphangiogenic nanoparticle. This contribution will be significant because the results may provide clinicians with a new strategy to improve kidney health and lower blood pressure in some of the ~148 million adults in the US with HTN.
项目总结/摘要 几乎每2个美国人中就有1人会患上高血压(HTN),而这些人中有一半会患上盐敏感症。 高血压(SSHTN)。精准医疗和新疗法,对抗心血管和肾脏疾病 HTN和SSHTN的并发症是非常需要的。长期目标是开发一种安全有效的 靶向肾淋巴管以减少肾损伤和HTN的治疗剂。这一目标 应用的目的是确定肾促红细胞生成剂在肾免疫细胞积累中的作用, 高血压性肾病的炎症反应以及增加肾功能是否能减轻肾损伤和降低血压。HTN 与活化的免疫细胞浸润到肾脏中相关,导致间质性炎症和肾损害。 损伤炎症的解决涉及淋巴管的增加,以清除间质免疫 细胞和液体,但淋巴反应不足导致持续的炎症和组织损伤。 肾脏中促炎免疫细胞的积累在HTN中起关键作用;然而, 尚不清楚HTN中的肾脏代谢。中心假设是(1)HTN刺激(盐,血管紧张素II, 不对称二甲基精氨酸)引起肾脏中的免疫细胞活化、浸润和炎症, 有助于肾功能代偿性增加,(2)肾间质液中的HTN刺激直接 影响肾淋巴细胞生物学和功能,以及(3)进一步增强肾功能足以 减轻肾损伤和HTN。最近的出版物和初步数据支持这些假设。的 假设将通过3个具体目标进行检验:(目标1)确定HTN中肾功能如何受到影响, (目的2)确定HTN刺激如何直接影响淋巴细胞生物学, 目的3:研究肾淋巴管生成对肾脏炎症和高血压的影响。 小鼠中肾脏代谢的药理学和遗传学扰动的各种组合以及 将使用淋巴细胞和分离的血管中的分子机制的检查。该研究还将 检查有和没有HTN的人的肾功能,以及开发和测试肾脏特异性 诱导淋巴管生成的纳米颗粒。本研究的创新之处在于阐明了 肾脏淋巴管在肾脏炎症和血压调节中的作用, 增强肾功能如何减少肾损伤和HTN。技术创新包括 开发独特的转基因小鼠和肾特异性淋巴管生成纳米颗粒。这一贡献 将是重要的,因为结果可能为临床医生提供一个新的策略,以改善肾脏健康, 降低美国约1.48亿HTN成年人的血压。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Time restricted feeding decreases renal innate immune cells and blood pressure in hypertensive mice.
  • DOI:
    10.1097/hjh.0000000000003200
  • 发表时间:
    2022-10-01
  • 期刊:
  • 影响因子:
    4.9
  • 作者:
  • 通讯作者:
Hypertension induces gonadal macrophage imbalance, inflammation, lymphangiogenesis, and dysfunction.
Update on Immune Mechanisms in Hypertension.
Hypertensive Stimuli Indirectly Stimulate Lymphangiogenesis through Immune Cell Secreted Factors.
  • DOI:
    10.3390/cells11142139
  • 发表时间:
    2022-07-07
  • 期刊:
  • 影响因子:
    6
  • 作者:
  • 通讯作者:
{{ 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 }}

BRETT M MITCHELL其他文献

BRETT M MITCHELL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('BRETT M MITCHELL', 18)}}的其他基金

Texas A&M College of Medicine Developing and Readying Underrepresented Minority Researchers (DRUMR) Summer Research Program
德克萨斯A
  • 批准号:
    10680395
  • 财政年份:
    2020
  • 资助金额:
    $ 39.62万
  • 项目类别:
Texas A&M College of Medicine Developing and Readying Underrepresented Minority Researchers (DRUMR) Summer Research Program
德克萨斯A
  • 批准号:
    10447171
  • 财政年份:
    2020
  • 资助金额:
    $ 39.62万
  • 项目类别:
Texas A&M College of Medicine Developing and Readying Underrepresented Minority Researchers (DRUMR) Summer Research Program
德克萨斯A
  • 批准号:
    10261491
  • 财政年份:
    2020
  • 资助金额:
    $ 39.62万
  • 项目类别:
Texas A&M College of Medicine Developing and Readying Underrepresented Minority Researchers (DRUMR) Summer Research Program
德克萨斯A
  • 批准号:
    10090921
  • 财政年份:
    2020
  • 资助金额:
    $ 39.62万
  • 项目类别:
Role of FKBP12/12.6 in Endothelial Function
FKBP12/12.6 在内皮功能中的作用
  • 批准号:
    7839416
  • 财政年份:
    2009
  • 资助金额:
    $ 39.62万
  • 项目类别:
Role of FKBP12/12.6 in Endothelial Function
FKBP12/12.6 在内皮功能中的作用
  • 批准号:
    7664949
  • 财政年份:
    2007
  • 资助金额:
    $ 39.62万
  • 项目类别:
Role of FKBP12/12.6 in Endothelial Function
FKBP12/12.6 在内皮功能中的作用
  • 批准号:
    7910682
  • 财政年份:
    2007
  • 资助金额:
    $ 39.62万
  • 项目类别:
Role of FKBP12/12.6 in Endothelial Function
FKBP12/12.6 在内皮功能中的作用
  • 批准号:
    7320563
  • 财政年份:
    2007
  • 资助金额:
    $ 39.62万
  • 项目类别:
Role of FKBP12/12.6 in Endothelial Function
FKBP12/12.6 在内皮功能中的作用
  • 批准号:
    7479587
  • 财政年份:
    2007
  • 资助金额:
    $ 39.62万
  • 项目类别:
Role of Immune Cells in Immunosuppressive Drug-Induced Hypertension
免疫细胞在免疫抑制药物诱发的高血压中的作用
  • 批准号:
    8732802
  • 财政年份:
    2006
  • 资助金额:
    $ 39.62万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 39.62万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了