Activated Protein C and Cardiac Inflammatory Response

活化蛋白 C 与心脏炎症反应

• 批准号: 10393231
• 负责人: Ji Li
• 金额: $ 1.49万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10393231
• 关键词: 5' -AMP-activated protein kinase; Address; Anti-Inflammatory Agents; Anticoagulants; Apoptotic; Attenuated; Cardiac; Cyclic AMP-Dependent Protein Kinases; Data; Enzymes; Heart; Heart Injuries; Hemorrhage; Inflammatory; Inflammatory Response; Ischemia; Lead; MAPK8 gene; Mediating; Metabolism; Mus; Myocardial; Myocardial Infarction; Myocardial Ischemia; Patients; Proteins; Recombinants; Reperfusion Injury; Reperfusion Therapy; Risk; Role; Signal Pathway; Signal Transduction; Stress; Testing; activated Protein C; cardioprotection; glucose transport; heart damage; ischemic injury; mortality; novel therapeutic intervention; response; stress activated protein kinase

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

项目成果

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: Frontiers in cardiovascular medicine
• 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: Biochemical and biophysical research communications
• 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

The Cardiac Dysfunction Caused by Metabolic Alterations in Alzheimer's Disease.

• DOI: 10.3389/fcvm.2022.850538
• 发表时间: 2022
• 期刊: Frontiers in cardiovascular medicine
• 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: Aging cell
• 影响因子: 7.8

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: Cells
• 影响因子: 6