Modulation of Natriuretic Peptides via Caveolin in Hypertrophy and Heart Failure.

通过 Caveolin 对肥大和心力衰竭中利尿钠肽的调节。

基本信息

  • 批准号:
    7931351
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-10-01 至 2014-09-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Project Summary/Abstract Cardiac hypertrophy is a critical determinant of cardiac remodeling and the progression of heart failure. Heart failure remains a major public health problem and effective therapies are limited. Molecular signaling involved in cardiac hypertrophy is complex and involves a number of cell surface receptors, signal transduction pathways and nuclear factors. An emerging theme in signal transduction is the concept of microdomains that contain cell surface receptors and intracellular signaling molecules and provide order to signaling pathways. Caveolae are specialized microdomains containing the structural proteins, caveolins that bind, organize and regulate receptors and signaling molecules involved in numerous cell functions including cell growth and hypertrophy. Knocking out the gene for the muscle specific isoform of caveolin (Caveolin-3, Cav-3) results in cardiac hypertrophy and cardiomyopathy. Conversely, overexpression of Cav-3 in cardiac myocytes blocks adrenergic agonist and endothelin-1 induced myocyte hypertrophy. Thus, loss of Cav-3 is sufficient to induce a molecular program resulting in cardiac hypertrophy and cardiomyopathy and overexpression of Cav-3 may be a means to negatively regulate cardiac hypertrophy. Atrial natriuretic peptide (ANP) has diuretic, natriuretic, and vasodilatory properties that inhibit cardiac hypertrophy. A relationship between ANP, caveolae and caveolins was proposed nearly two decades ago. ANP is present within caveolae, closely associated with Cav-3 and may be secreted via caveolae from cardiac myocytes. The preliminary data show that cardiac myocyte-specific overexpression of Cav-3 produces a cardiac phenotype with dramatically increased expression of ANP in the left ventricle at baseline and a reduction in cardiac hypertrophy, increased survival and preserved cardiac function in the face of left ventricular pressure overload. The proposal is designed to address the hypothesis that Cav-3 modulates ANP expression to reduce cardiac hypertrophy and heart failure and to evaluate overexpression of Cav-3 as a unique and beneficial means to modulate ANP expression and treat heart failure patients. The following aims will be pursued: Aim 1: Will determine mechanisms for Cav-3 modulation of ANP and ANP coupled signaling in cardiac hypertrophy and heart failure. Aim 2: Will determine if conditional cardiac myocyte-specific overexpression of Cav-3 modulates ANP and ameliorates heart failure induced by pressure overload. Aim 3: Will determine if gene transfer of Cav-3 modulates ANP and shows efficacy in a preclinical model of heart failure in swine. State of the art molecular and physiological techniques will be used in the studies in clinically relevant models of hypertrophy and heart failure in large and small animal models to focus on mechanism and produce important preclinical data to support potential clinical trials on caveolins as novel therapeutics for heart failure patients. PUBLIC HEALTH RELEVANCE: Project Narrative Prevalent cardiovascular diseases such as chronic hypertension and ischemic heart disease result in cardiac hypertrophy and the development of congestive heart failure. Heart failure is associated with high mortality and morbidity and poor quality of life. Heart failure affects nearly 5 million Americans and is listed on 1 out of every 8 death-certificates in the United States. Heart failure is a primary focus of the VA quality enhancement research initiative (QUERI) and remains the number one discharge diagnosis in the VA healthcare system. The work described in this proposal focuses on elucidating mechanisms to support the use of caveolin proteins as novel therapeutic targets for heart failure patients and is of relevance to the VA patient care mission.
描述(由申请人提供):

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 }}

DAVID M ROTH其他文献

DAVID M ROTH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('DAVID M ROTH', 18)}}的其他基金

Exosomes in aging and operative hypothermic circulatory arrest
外泌体在衰老和手术低温停循环中的作用
  • 批准号:
    9766174
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
ShEEP Request for Vevo 3100 Imaging System
ShEEP 请求 Vevo 3100 成像系统
  • 批准号:
    9213727
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
Integrins and Caveolin Proteins in Cardiac Hypertrophy and Failure
整合素和小窝蛋白在心脏肥大和衰竭中的作用
  • 批准号:
    8535411
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Integrins and Caveolin Proteins in Cardiac Hypertrophy and Failure
整合素和小窝蛋白在心脏肥大和衰竭中的作用
  • 批准号:
    8726471
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Integrins and Caveolin Proteins in Cardiac Hypertrophy and Failure
整合素和小窝蛋白在心脏肥大和衰竭中的作用
  • 批准号:
    8842694
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Integrins and Caveolin Proteins in Cardiac Hypertrophy and Failure
整合素和小窝蛋白在心脏肥大和衰竭中的作用
  • 批准号:
    9061810
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Modulation of Natriuretic Peptides via Caveolin in Hypertrophy and Heart Failure.
通过 Caveolin 对肥大和心力衰竭中利尿钠肽的调节。
  • 批准号:
    8196337
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Modulation of Natriuretic Peptides via Caveolin in Hypertrophy and Heart Failure.
通过 Caveolin 对肥大和心力衰竭中利尿钠肽的调节。
  • 批准号:
    8597371
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Enhancing Cardiac Protection
加强心脏保护
  • 批准号:
    9339498
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Modulation of Natriuretic Peptides via Caveolin in Hypertrophy and Heart Failure.
通过 Caveolin 对肥大和心力衰竭中利尿钠肽的调节。
  • 批准号:
    8391592
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:

相似海外基金

Alteration of collagen synthesis and cross-link profile by beta-adrenergic agonists
β-肾上腺素能激动剂改变胶原合成和交联特征
  • 批准号:
    RGPIN-2014-06641
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Individual
Alteration of collagen synthesis and cross-link profile by beta-adrenergic agonists
β-肾上腺素能激动剂改变胶原合成和交联特征
  • 批准号:
    RGPIN-2014-06641
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Individual
Alteration of collagen synthesis and cross-link profile by beta-adrenergic agonists
β-肾上腺素能激动剂改变胶原合成和交联特征
  • 批准号:
    RGPIN-2014-06641
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Individual
Alteration of collagen synthesis and cross-link profile by beta-adrenergic agonists
β-肾上腺素能激动剂改变胶原合成和交联特征
  • 批准号:
    RGPIN-2014-06641
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Individual
Development of a new pharmacotherapy for heart failure using alpha-2 adrenergic agonists
使用 α-2 肾上腺素能激动剂开发治疗心力衰竭的新药物疗法
  • 批准号:
    15K09110
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Alteration of collagen synthesis and cross-link profile by beta-adrenergic agonists
β-肾上腺素能激动剂改变胶原合成和交联特征
  • 批准号:
    RGPIN-2014-06641
  • 财政年份:
    2014
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Individual
Reversing oxidative inhibition of the Na-K pump by beta3 adrenergic agonists: implications for heart failure therapy
β3 肾上腺素能激动剂逆转 Na-K 泵的氧化抑制:对心力衰竭治疗的影响
  • 批准号:
    nhmrc : 633252
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
    NHMRC Project Grants
Research of the molecular mechanism in effects of doping drugs(adrenergic agonists)
兴奋剂药物(肾上腺素激动剂)作用的分子机制研究
  • 批准号:
    21500628
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
EFFECTS OF ALPHA2-ADRENERGIC AGONISTS AND NMDA-ANTAGONISTS ON CEREBRAL MICROCIRCULATION UNDER THE HYPOTHERMIC CONDITION -ASSESSED WITH CLOSED CRANIAL WINDOW TECHNIQUE-.
α2-肾上腺素能激动剂和 NMDA 拮抗剂对低温条件下脑微循环的影响 - 用闭颅窗技术评估 -。
  • 批准号:
    11671489
  • 财政年份:
    1999
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
EFFECTS OF NMDA-ATAGONISTS AND ALPHA2-ADRENERGIC AGONISTS ON SPINAL AND CEREBRAL MICROCIRCULATION -ASSESSED WITH CLOSED SPINAL AND CRANIAL WINDOW TECHNIQUE-.
NMDA 激动剂和 α2 肾上腺素能激动剂对脊髓和大脑微循环的影响 - 使用闭合脊柱和颅窗技术进行评估 -。
  • 批准号:
    09671555
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了