Troponin I phosphorylation as a novel novel cardiac inotrope

肌钙蛋白 I 磷酸化作为一种​​新型强心剂

基本信息

  • 批准号:
    10660193
  • 负责人:
  • 金额:
    $ 67.12万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-04-01 至 2027-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY In heart disease, the amount of blood pumped by the heart is not sufficient to supply the metabolic demands of the body. Current positive inotropes (dobutamine, milrinone) increase cardiac contraction by elevating the intracellular calcium contractile signal, however trials have demonstrated this elevated intracellular calcium also causes detrimental arrhythmia, impaired relaxation, and increased mortality rendering this inotropic approach unsuccessful as a long-term therapy. There are currently no approved therapies that directly increase the insufficient function of the heart in disease without long-term detrimental effects. The myofilament protein troponin I (TnI) is critical to relay the calcium activating signal into muscle contraction and is therefore a key regulator of in vivo cardiac muscle function. We have shown the site-specific phosphorylation of TnI increases cardiac muscle contraction without elevating intracellular calcium. Our preliminary data now demonstrates this TnI phosphorylation increases in vivo cardiac function in both normal and diseased hearts without long-term detrimental effects. This proposal will establish the novel effects and mechanism of this TnI site-specific phosphorylation to improve in vivo cardiac function in the normal and diseased mouse heart. We will further establish the effects and safety of this site-specific TnI phosphorylation on human cardiac tissue towards establishing this phosphorylation as a future therapeutic approach in human heart disease.
项目总结

项目成果

期刊论文数量(0)
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Brandon J Biesiadecki其他文献

Brandon J Biesiadecki的其他文献

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{{ truncateString('Brandon J Biesiadecki', 18)}}的其他基金

Training to provide the knowledge, skills, and culture to the next generation of cardiovascular scientists
为下一代心血管科学家提供知识、技能和文化的培训
  • 批准号:
    10331226
  • 财政年份:
    2017
  • 资助金额:
    $ 67.12万
  • 项目类别:
Training to provide the knowledge, skills, and culture to the next generation of cardiovascular scientists
为下一代心血管科学家提供知识、技能和文化的培训
  • 批准号:
    10602446
  • 财政年份:
    2017
  • 资助金额:
    $ 67.12万
  • 项目类别:
Integrated crosstalk of thin filament post-translational modifications
细丝翻译后修饰的综合串扰
  • 批准号:
    9061802
  • 财政年份:
    2013
  • 资助金额:
    $ 67.12万
  • 项目类别:
Integrated crosstalk of thin filament post-translational modifications
细丝翻译后修饰的综合串扰
  • 批准号:
    8726470
  • 财政年份:
    2013
  • 资助金额:
    $ 67.12万
  • 项目类别:
Integrated crosstalk of thin filament post-translational modifications
细丝翻译后修饰的综合串扰
  • 批准号:
    8851003
  • 财政年份:
    2013
  • 资助金额:
    $ 67.12万
  • 项目类别:
Integrated crosstalk of thin filament post-translational modifications
细丝翻译后修饰的综合串扰
  • 批准号:
    8504053
  • 财政年份:
    2013
  • 资助金额:
    $ 67.12万
  • 项目类别:
Integrated Crosstalk of Thin Filament Post-translational Modifications
细丝翻译后修饰的综合串扰
  • 批准号:
    9448622
  • 财政年份:
    2013
  • 资助金额:
    $ 67.12万
  • 项目类别:
Integrated Crosstalk of Thin Filament Post-translational Modifications
细丝翻译后修饰的综合串扰
  • 批准号:
    10192786
  • 财政年份:
    2013
  • 资助金额:
    $ 67.12万
  • 项目类别:
Post-translational Modification in Cardiac Muscle
心肌翻译后修饰
  • 批准号:
    8115759
  • 财政年份:
    2009
  • 资助金额:
    $ 67.12万
  • 项目类别:
Post-translational Modification in Cardiac Muscle
心肌翻译后修饰
  • 批准号:
    7939634
  • 财政年份:
    2009
  • 资助金额:
    $ 67.12万
  • 项目类别:

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