CYTOSKELETON AND CONTRACTILE DYSFUNCTION IN HYPERTROPHY

肥大症中的细胞骨架和收缩功能障碍

基本信息

  • 批准号:
    6631281
  • 负责人:
  • 金额:
    $ 29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-08-01 至 2003-07-31
  • 项目状态:
    已结题

项目摘要

The initial goals of this project were to determine whether cytoskeletal alterations have a role in the contractile dysfunction of hypertrophied myocardium, and if so, what is their nature, their locus, and their cause. Important accomplishments have been 1) the demonstration of microtubule- based contractile dysfunction in cardiocytes from the hypertrophied and failing RV and LV, 2) extension of these findings to isolated tissue and to the intact heart, 3) biophysical characterization of the etiology of the microtubule-based contractile dysfunction, 4) the finding that this pathophysiological mechanism is tightly restricted to pressure overload- induced hypertrophy in which wall stress is increased, 5) the demonstration that microtubules are the only major extra-myofilament cytoskeletal protein so affected, 6) the finding that this phenomenon is based both on increased tubulin, and thus microtubules, and on increased stability of the microtubules once formed, 7) the finding that the major cardiac microtubule-stabilizing protein is markedly up-regulated in pressure overload cardiac hypertrophy, 8) the finding that transcriptional upregulation of two minor beta-tubulin isoforms during hypertrophy, which we found to mimic the developmental regulation of these genes, accounts for the increase in beta-tubulin, and 9) the demonstration that one of these isoforms may act synergistically with MAP 4 to stabilize microtubules in pressure overload cardiac hypertrophy. The first goal of the work proposed is to reduce the correlative relationship between microtubule network densification and cardiac contractile dysfunction to a cause-and-effect relationship via direct genetic manipulation of microtubule stability and via an exploration of the role of altered expression of genes encoding microtubule and microtubule-associated proteins found to date. The second goal is to extend this investigation from microtubule effects on cardiocyte constitutive properties to a consideration of more specific microtubule-dependent effects on cardiocyte constitutive properties to a consideration of more specific microtubule- dependent effects on the hypertrophied cell, and explicitly, a consideration of any role of increased density of the cardiocyte microtubule network in the beta-adrenergic receptor desensitization characteristic of cardiac hypertrophy.
该项目的最初目标是确定细胞骨架

项目成果

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GEORGE COOPER其他文献

GEORGE COOPER的其他文献

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{{ truncateString('GEORGE COOPER', 18)}}的其他基金

Beta-Adrenergic Control of the Pathological Cardiac Microtubule Network
病理性心脏微管网络的β-肾上腺素能控制
  • 批准号:
    8111961
  • 财政年份:
    2010
  • 资助金额:
    $ 29万
  • 项目类别:
MAP4 REGULATION OF CARDIAC MICROTUBULE NETWORK DENSITY
MAP4 心脏微管网络密度的调节
  • 批准号:
    8063058
  • 财政年份:
    2010
  • 资助金额:
    $ 29万
  • 项目类别:
Beta-Adrenergic Control of the Pathological Cardiac Microtubule Network
病理性心脏微管网络的β-肾上腺素能控制
  • 批准号:
    7952783
  • 财政年份:
    2010
  • 资助金额:
    $ 29万
  • 项目类别:
MAP4 REGULATION OF CARDIAC MICROTUBULE NETWORK DENSITY
MAP4 心脏微管网络密度的调节
  • 批准号:
    7885169
  • 财政年份:
    2010
  • 资助金额:
    $ 29万
  • 项目类别:
Connexin Distribution in Physiological Versus Pathological Cardiac Hypertrophy
生理性与病理性心脏肥大中的连接蛋白分布
  • 批准号:
    8195558
  • 财政年份:
    2009
  • 资助金额:
    $ 29万
  • 项目类别:
Connexin Distribution in Physiological Versus Pathological Cardiac Hypertrophy
生理性与病理性心脏肥大中的连接蛋白分布
  • 批准号:
    7903963
  • 财政年份:
    2009
  • 资助金额:
    $ 29万
  • 项目类别:
Connexin Distribution in Physiological Versus Pathological Cardiac Hypertrophy
生理性与病理性心脏肥大中的连接蛋白分布
  • 批准号:
    7788252
  • 财政年份:
    2009
  • 资助金额:
    $ 29万
  • 项目类别:
CYTOSKELETON AND CONTRACTILE DYSFUNCTION IN HYPERTROPHY
肥大症中的细胞骨架和收缩功能障碍
  • 批准号:
    6808267
  • 财政年份:
    2003
  • 资助金额:
    $ 29万
  • 项目类别:
ADMINISTRATIVE CORE
行政核心
  • 批准号:
    6808272
  • 财政年份:
    2003
  • 资助金额:
    $ 29万
  • 项目类别:
CORE--CELL ISOLATION AND CULTURE
核心——细胞分离与培养
  • 批准号:
    6808274
  • 财政年份:
    2003
  • 资助金额:
    $ 29万
  • 项目类别:

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