Activated Protein C and Cardiac Inflammatory Response

活化蛋白 C 与心脏炎症反应

基本信息

  • 批准号:
    10393231
  • 负责人:
  • 金额:
    $ 1.49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-05-01 至 2023-02-28
  • 项目状态:
    已结题

项目摘要

Abstract Activated protein C (APC) was first identified as a natural anticoagulant enzyme. Besides its anti- coagulant activity, APC exerts cytoprotective effects such as anti-inflammatory and anti-apoptosis. It has revealed that APC reduces the mortality rate and apoptotic rate during cardiac ischemia and reperfusion. However, the mechanism involved in cardioprotection stimulated by APC is still unclear. The objective of this project is to illustrate the mechanism by which APC mediates cardioprotection against ischemic injury. Our preliminary data demonstrated that the administration of APC reduced myocardial infarction during ischemia and reperfusion. AMP-activated protein kinase (AMPK), a cardioprotective signaling, was activated in APC treated mouse heart. Moreover, ischemia and reperfusion-induced stress-activated protein kinase (SAPK/JNK) signaling was attenuated by APC treatment. We hypothesize that APC protects against myocardial ischemic injury by triggering crucial signaling pathways to modulate substrates metabolism and reducing inflammatory response under ischemic stress. Three specific aims will be addressed to test the hypothesis: 1) determine the modulation of AMP activated protein kinase signaling by APC derivatives during ischemia and reperfusion in the heart; 2) determine the effect of APC derivatives on inflammatory response during ischemia and reperfusion in the heart; 3) determine the mechanisms by which APC modulates glucose transport that reduces ROS responsible inflammatory response in the ischemic heart. APC may decrease the pro-inflammatory factors during cardiac ischemia and reperfusion to reduce heart injury. We also will figure out whether anticoagulant domain of APC is not important for its cardioprotction against ischemia and reperfusion injury, which will provide evidence that recombinant APC without anticoagulant activity can be used for therapy of ischemic heart disease without risk of bleeding.
摘要 活化蛋白C(APC)是一种天然的抗凝血酶。除了它的反- APC具有凝血活性,具有抗炎、抗凋亡等细胞保护作用。它有 提示APC可降低心肌缺血再灌流时的死亡率和凋亡率。 然而,APC刺激心肌保护的机制尚不清楚。这样做的目的是 该项目旨在阐明APC介导的心肌保护机制,以对抗缺血损伤。我们的 初步数据显示,给予APC可减少缺血期间的心肌梗死和 再灌流。心肌保护信号--AMPK在APC治疗中被激活 老鼠的心。此外,缺血和再灌注诱导的应激激活蛋白激酶(SAPK/JNK)信号转导 经APC处理后减弱。我们假设APC通过以下途径保护心肌缺血损伤 触发调节底物代谢和减少炎症反应的关键信号通路 在缺血应激状态下。三个具体的目标将被用来检验假设:1)确定调制 APC衍生物在心脏缺血再灌注中对AMP激活的蛋白激酶信号的影响;2) 测定APC衍生物对心脏缺血再灌流时炎症反应的影响; 3)确定APC调节葡萄糖转运从而降低ROS的机制 缺血心脏的炎症反应。APC可能降低心脏手术中的促炎因子 缺血再灌流可减少心脏损伤。我们还将计算APC的抗凝血区是否为 对其抗缺血再灌注损伤的心脏保护作用并不重要,这将提供证据 无抗凝活性的重组APC可用于无风险的缺血性心脏病的治疗 失血过多。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
STK35 Gene Therapy Attenuates Endothelial Dysfunction and Improves Cardiac Function in Diabetes.
  • DOI:
    10.3389/fcvm.2021.798091
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    3.6
  • 作者:
    Joladarashi D;Zhu Y;Willman M;Nash K;Cimini M;Thandavarayan RA;Youker KA;Song X;Ren D;Li J;Kishore R;Krishnamurthy P;Wang L
  • 通讯作者:
    Wang L
Sirtuin 1 aggravates hypertrophic heart failure caused by pressure overload via shifting energy metabolism.
  • DOI:
    10.1016/j.bbrc.2022.11.014
  • 发表时间:
    2022-11
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Tran Ngoc Van Le;L. Zoungrana;Hao Wang;M. Fatmi;Di Ren;Meredith Krause-Hauch;Ji Li
  • 通讯作者:
    Tran Ngoc Van Le;L. Zoungrana;Hao Wang;M. Fatmi;Di Ren;Meredith Krause-Hauch;Ji Li
The Cardiac Dysfunction Caused by Metabolic Alterations in Alzheimer's Disease.
  • DOI:
    10.3389/fcvm.2022.850538
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    3.6
  • 作者:
    Murphy J;Le TNV;Fedorova J;Yang Y;Krause-Hauch M;Davitt K;Zoungrana LI;Fatmi MK;Lesnefsky EJ;Li J;Ren D
  • 通讯作者:
    Ren D
Cardiomyocyte Pdk4 response is associated with metabolic maladaptation in aging.
心肌细胞PDK4反应与衰老中的代谢不良有关。
  • DOI:
    10.1111/acel.13800
  • 发表时间:
    2023-04
  • 期刊:
  • 影响因子:
    7.8
  • 作者:
  • 通讯作者:
Targeting on Nrf2/Sesn2 Signaling to Rescue Cardiac Dysfunction during High-Fat Diet-Induced Obesity.
  • DOI:
    10.3390/cells11162614
  • 发表时间:
    2022-08-22
  • 期刊:
  • 影响因子:
    6
  • 作者:
  • 通讯作者:
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Ji Li其他文献

Ji Li的其他文献

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{{ truncateString('Ji Li', 18)}}的其他基金

A Stress Inducible Protein Sestrin2 in Heart Failure
心力衰竭中的应激诱导蛋白 Sestrin2
  • 批准号:
    10616476
  • 财政年份:
    2022
  • 资助金额:
    $ 1.49万
  • 项目类别:
A Stress Inducible Protein Sestrin2 in Heart Failure
心力衰竭中的应激诱导蛋白 Sestrin2
  • 批准号:
    10363811
  • 财政年份:
    2022
  • 资助金额:
    $ 1.49万
  • 项目类别:
A Stress Inducible Protein Sestrin2 in Heart Failure
心力衰竭中的应激诱导蛋白 Sestrin2
  • 批准号:
    11002402
  • 财政年份:
    2022
  • 资助金额:
    $ 1.49万
  • 项目类别:
Activated Protein C in Acute Injury
急性损伤中的活化蛋白 C
  • 批准号:
    10475352
  • 财政年份:
    2022
  • 资助金额:
    $ 1.49万
  • 项目类别:
MIF and Cardiovascular Inflammation
MIF 与心血管炎症
  • 批准号:
    10269328
  • 财政年份:
    2021
  • 资助金额:
    $ 1.49万
  • 项目类别:
MIF and Cardiovascular Inflammation
MIF 与心血管炎症
  • 批准号:
    10827626
  • 财政年份:
    2021
  • 资助金额:
    $ 1.49万
  • 项目类别:
MIF and Cardiovascular Inflammation
MIF 与心血管炎症
  • 批准号:
    10450128
  • 财政年份:
    2021
  • 资助金额:
    $ 1.49万
  • 项目类别:
Activated Protein C and Cardiac Inflammatory Response
活化蛋白 C 与心脏炎症反应
  • 批准号:
    10004784
  • 财政年份:
    2018
  • 资助金额:
    $ 1.49万
  • 项目类别:
AMPK-SIRT1 Signaling in the Adaptive Metabolic Response
适应性代谢反应中的 AMPK-SIRT1 信号传导
  • 批准号:
    9114282
  • 财政年份:
    2015
  • 资助金额:
    $ 1.49万
  • 项目类别:
AMPK-SIRT1 Signaling in the Adaptive Metabolic Response
适应性代谢反应中的 AMPK-SIRT1 信号传导
  • 批准号:
    9243202
  • 财政年份:
    2015
  • 资助金额:
    $ 1.49万
  • 项目类别:

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AMP 激活蛋白激酶对 1 型糖尿病免疫细胞调节的药理学靶向
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AMP 激活的蛋白激酶在引起 GVHD 的 T 细胞中的作用
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