Asporin, an extracellular protein, regulates cardiac remodeling

阿孢菌素是一种细胞外蛋白,调节心脏重塑

基本信息

  • 批准号:
    10441587
  • 负责人:
  • 金额:
    $ 41.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2026-06-30
  • 项目状态:
    未结题

项目摘要

Project Summary Extracellular matrix (ECM) is critical during cardiac remodeling in altering the cell’s response. Recently, class I small leucine rich proteoglycans (SLRPs) showed enormous impact on the heart’s function during ischemic injury or cardiac remodeling. Adverse cardiac remodeling stimulates fibrotic scar deposition due to increased TGFβ activity on fibroblasts. In the last decade, a non-conventional class I SLRP protein, asporin (ASPN), has been shown to play a role in regulating TGFβ signaling and cell viability in cancer and osteoporosis. The biological impact of ASPN in regulating TGFβ and cell viability in heart is unknown. Our long-term goal is to dissect the detailed mechanisms regulating ASPN activity and its impact on fibroblasts and cardiomyocytes, particularly in the setting of cardiac remodeling. These discoveries will facilitate design of effective ASPN-based therapies for heart failure. The objective of this grant is to characterize the role of ASPN in fibrosis and cardiomyocyte cell viability. Our central hypothesis is that ASPN is released by fibroblasts during cardiac stress and inhibits TGFβ signaling to reduce fibrosis during cardiac remodeling. Further, released ASPN acts on cardiomyocytes to upregulate autophagy and prevent cell death. Our rationale is that identification of the mechanisms to stimulate ASPN-protective effects in cardiac remodeling will offer new therapeutic opportunities. This project will further test therapeutic peptide delivery as well as AAV9-mediated delivery of ASPN gene for efficacy in mitigating reperfusion injury and cardiac remodeling. Our specific aims will test the following hypotheses: (Aim 1) ASPN inhibits fibrosis to maintain cardiac function and prevents adverse cardiac remodeling; (Aim 2) ASPN induces autophagy in cardiomyocytes; (Aim 3) ASPN regulates cardiomyocyte cell death in the setting of ischemia- reperfusion injury. Upon conclusion, we will better understand the role of novel role of ASPN in inhibiting fibrosis and activating autophagy for beneficial cardiac remodeling. This contribution is significant since it will establish the several pathways targeted by ASPN from ECM to fibroblasts and cardiomyocytes. Furthermore, current therapies, while promising in limiting ischemic injury, fail to address the key issue of adverse cardiac remodeling in heart failure patients. The proposed research is innovative as we will investigate the effects of ASPN in regulating fibrosis and cardiomyocyte cell death, an unexamined process to date. Insight into the mechanisms of ASPN activity will pave the way for ASPN-based therapies to benefit cardiac remodeling.
项目总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Sarah J Parker其他文献

Influenza vaccination coverage among an urban pediatric asthma Influenza vaccination coverage among an urban pediatric asthma population: Implications for population health population: Implications for population health
城市儿童哮喘人群的流感疫苗接种覆盖率 城市儿童哮喘人群的流感疫苗接种覆盖率:对人口健康的影响 人口:对人口健康的影响
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Sarah J Parker;Amy M DeLaroche;Alex B. Hill;Rajan Arora;ID JulieGleason
  • 通讯作者:
    ID JulieGleason
Clinical factors associated with the use of dexamethasone for asthma in the pediatric emergency department
儿科急诊室使用地塞米松治疗哮喘的相关临床因素
  • DOI:
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    1.9
  • 作者:
    Amy M DeLaroche;F. Mowbray;Sarah J Parker;Y. Ravichandran;A. Jones
  • 通讯作者:
    A. Jones
Monitoring Diagnostic Safety Risks in Emergency Departments: Protocol for a Machine Learning Study
监测急诊科的诊断安全风险:机器学习研究协议
  • DOI:
    10.2196/preprints.24642
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    1.7
  • 作者:
    Moein Enayati;M. Sir;Xingyu Zhang;Sarah J Parker;Elizabeth Duffy;Hardeep Singh;P. Mahajan;K. Pasupathy
  • 通讯作者:
    K. Pasupathy

Sarah J Parker的其他文献

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{{ truncateString('Sarah J Parker', 18)}}的其他基金

Mechanisms of sex-biased risk and resiliency in aneurysm and dissection
动脉瘤和夹层的性别偏见风险和弹性机制
  • 批准号:
    10705715
  • 财政年份:
    2022
  • 资助金额:
    $ 41.75万
  • 项目类别:
Mechanisms of sex-biased risk and resiliency in aneurysm and dissection
动脉瘤和夹层的性别偏见风险和弹性机制
  • 批准号:
    10532033
  • 财政年份:
    2022
  • 资助金额:
    $ 41.75万
  • 项目类别:
Asporin, an extracellular protein, regulates cardiac remodeling
阿孢菌素是一种细胞外蛋白,调节心脏重塑
  • 批准号:
    10658863
  • 财政年份:
    2021
  • 资助金额:
    $ 41.75万
  • 项目类别:
Mapping the Angiotensin II-TGFB-Integrin signaling triad to reveal therapeutic targets in aortic aneurysm
绘制血管紧张素 II-TGFB-整合素信号三联体图谱以揭示主动脉瘤的治疗靶点
  • 批准号:
    9108213
  • 财政年份:
    2016
  • 资助金额:
    $ 41.75万
  • 项目类别:
Mapping the Angiotensin II-TGFB-Integrin signaling triad to reveal therapeutic targets in aortic aneurysm
绘制血管紧张素 II-TGFB-整合素信号三联体图谱以揭示主动脉瘤的治疗靶点
  • 批准号:
    9274098
  • 财政年份:
    2016
  • 资助金额:
    $ 41.75万
  • 项目类别:

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骨骼合成代谢过程中骨-脂肪相互作用
  • 批准号:
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  • 财政年份:
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骨骼合成代谢过程中骨-脂肪相互作用
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