The Role of Acetyl-CoA Metabolism in Epigenetic Regulation of Myofibroblast Differentiation

乙酰辅酶A代谢在肌成纤维细胞分化的表观遗传调控中的作用

基本信息

  • 批准号:
    10684688
  • 负责人:
  • 金额:
    $ 5.27万
  • 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:
    2020-09-01 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT A common feature of heart failure (HF) is excessive extracellular matrix deposition by a specialized and differentiated fibroblast population, known as myofibroblasts, in response to cardiac injury. While myofibroblasts help to maintain the structural integrity of the injured heart and prevent ventricular wall rupture, persistence of myofibroblasts results in excessive fibrosis and subsequent cardiac decompensation. Therefore, identifying molecular mechanisms of myofibroblast differentiation in cardiac fibrosis could yield novel clinical targets to delay or reverse the development of HF. Recent evidence suggests metabolism may drive cellular differentiation through the modulation of epigenetic-modifying enzymes that enhance or silence genes associated with cellular differentiation. Altered metabolism changes the concentration of metabolites that act as substrates for epigenetically modifying enzymes, such as the changing levels of acetyl-CoA that alter the activity of histone acetyltransferases (HAT). Our preliminary data indicate that increased glycolytic rate is a key feature driving myofibroblast differentiation. We identified metabolic regulation of histone demethylation as a feature of myofibroblast differentiation and we now turn our sights to histone acetylation as an epigenetic modification permissive of myofibroblast gene expression. This proposal hypothesizes that increased acetyl-CoA biosynthesis is necessary for histone lysine acetylation by HATs during differentiation for the transcriptional activation of the myofibroblast gene program. This study seeks to identify novel therapeutic targets to mitigate the consequences of fibrosis in HF.
项目总结/文摘

项目成果

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Michael Lazaropoulos其他文献

Michael Lazaropoulos的其他文献

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{{ truncateString('Michael Lazaropoulos', 18)}}的其他基金

The Role of Acetyl-CoA Metabolism in Epigenetic Regulation of Myofibroblast Differentiation
乙酰辅酶A代谢在肌成纤维细胞分化的表观遗传调控中的作用
  • 批准号:
    10464881
  • 财政年份:
    2020
  • 资助金额:
    $ 5.27万
  • 项目类别:
The Role of Acetyl-CoA Metabolism in Epigenetic Regulation of Myofibroblast Differentiation
乙酰辅酶A代谢在肌成纤维细胞分化的表观遗传调控中的作用
  • 批准号:
    10471443
  • 财政年份:
    2020
  • 资助金额:
    $ 5.27万
  • 项目类别:
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